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Mechanism of interaction between autophagy and apoptosis in cancer

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Abstract

The mechanisms of two programmed cell death pathways, autophagy, and apoptosis, are extensively focused areas of research in the context of cancer. Both the catabolic pathways play a significant role in maintaining cellular as well as organismal homeostasis. Autophagy facilitates this by degradation and elimination of misfolded proteins and damaged organelles, while apoptosis induces canonical cell death in response to various stimuli. Ideally, both autophagy and apoptosis have a role in tumor suppression, as autophagy helps in eliminating the tumor cells, and apoptosis prevents their survival. However, as cancer proceeds, autophagy exhibits a dual role by enhancing cancer cell survival in response to stress conditions like hypoxia, thereby promoting chemoresistance to the tumor cells. Thus, any inadequacy in either of their levels can lead to tumor progression. A complex array of biomarkers is involved in maintaining coordination between the two by acting as either positive or negative regulators of one or both of these pathways of cell death. The resulting crosstalk between the two and its role in influencing the survival or death of malignant cells makes it quintessential, among other challenges facing chemotherapeutic treatment of cancer. In view of this, the present review aims to highlight some of the factors involved in maintaining their diaphony and stresses the importance of inhibition of cytoprotective autophagy and deletion of the intermediate pathways involved to facilitate tumor cell death. This will pave the way for future prospects in designing drug combinations facilitating the synergistic effect of autophagy and apoptosis in achieving cancer cell death.

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Abbreviations

CMA:

Chaperone-Mediated Autophagy

mTOR:

Mammalian Target of Rapamycin

mTORC1:

Mammalian Target of Rapamycin Complex 1

mTORC2:

Mammalian Target of Rapamycin Complex 2

ATG:

Autophagy Related Protein

AMP:

Adenosine Monophosphate

AMPK:

AMP-Activated Protein Kinase

ULK:

Unc-51-Like Autophagy-Activating Kinase

PI3K:

Phosphatidyl Inositol-3 Kinase

BCL-2:

B-Cell Lymphoma 2

LC3:

Light Chain Kinase 3

VPS:

Vacuolar Protein Sorting

SNARE:

Soluble n-Ethylmaleimide Sensitive Factor Attachment Protein Receptor

PE:

Phosphatidylethanolamine

AVO:

Acidic Vesicular Organelles

UVRAG:

UV Radiation Resistance Associated Gene

FIP200:

Focal Adhesion Kinase Family Interacting Protein of 200 Kd

PTEN:

Phosphatase and Tensin Analogue

HIF:

Hypoxia Inducible Factors

BNIP3:

BCL2/Adenovirus E1B 19 kDa Protein-Interacting Protein 3

MOMP:

Mitochondrial Outer Membrane Permeabilization

DNA:

Deoxyribonucleic Acid

APAF1:

Apoptotic Protease-Activating Factor 1

ATP:

Adenosine Triphosphate

TNFR1:

Tumor Necrosis Factor Receptor 1

TRAIL:

Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand

TRAILR:

TNF-Related Apoptosis-Inducing Ligand Receptor

TRADD:

TNFR1-Associated Death Domain

FADD:

Fas-Associated Death Domain

MEK:

Mitogen-Activated Protein Kinase Kinase

IAP:

Inhibitors of Apoptosis Proteins

CD95:

Cluster of Differentiation 95

BAX:

BCL-2-Associated X Protein

BAK:

BCL-2 Antagonist or Killer

UPR:

Unfolded Protein Response

ER:

Endoplasmic Reticulum

BID:

BH3-Interacting Domain Death Agonist

VMP1:

Vacuole Membrane Protein 1

AMBRA1:

Activating Molecule Beclin1-Regulated Autophagy 1

BCLAF1:

BCL-2-Associated Transcription Factor 1

SKI:

Sphingosine Kinase Inhibitor

p53:

Tumor Protein 53

DRAM:

Damage-Regulated Autophagy Modulator

IFNγ:

Interferon Gamma

MOMP:

Mitochondrial Outer Membrane Permeabilization

Bcl-xl:

B-Cell Lymphoma Extra-Large

BAD:

BCL2 Associated Agonist of Cell Death

Akt:

Protein Kinase B

c-FLIP:

Cellular FLICE (FADD-like IL-1β-Converting Enzyme)-Inhibitory Protein

DAPK:

Death Associated Protein Kinase

PARP:

Poly (ADP-Ribose) Polymerase

APAF1:

Apoptotic Protease Activating Factor 1

ATP:

Adenosine Triphosphate

SMAC:

Second Mitochondria-Derived Activator of Caspase

RIP:

Receptor Interacting Protein

NF-κB:

Nuclear Factor Kappa Light Chain Enhancer of Activated B Cells

ROS:

Reactive Oxygen Species

PUMA:

p53 Upregulated Modulator of Apoptosis

BIM:

B-Cell Lymphoma 2-Interacting Mediator

Mcl-1:

Myeloid Cell Leukaemia 1

DRAM:

Damage-Regulated Autophagy Modulator

FAP-1:

Fas-Associated Phosphatase-1

RTK:

Receptor Tyrosine Kinase

References

  1. World Health Organisation (2018) Cancer, fact sheets. World Health Organisation, Geneva

    Google Scholar 

  2. American Cancer Society (2020) Cancer facts & fig. American Cancer Society, Atlanta

    Google Scholar 

  3. Cancer Statistics—India Against Cancer (2020) https://doi.org/http://cancerindia.org.in/cancer-statistics/

  4. Liu J, Lin M, Yu J, Liu B, Bao J (2011) Targeting apoptotic and autophagic pathways for cancer therapeutics. Cancer Lett 300:105–114. https://doi.org/10.1016/j.canlet.2010.10.001

    Article  CAS  PubMed  Google Scholar 

  5. Colhado Rodrigues BL, Lallo MA, Perez EC (2020) The controversial role of autophagy in tumor development: a systematic review. Immunol Invest 49:386–396. https://doi.org/10.1080/08820139.2019.1682600

    Article  CAS  PubMed  Google Scholar 

  6. Hseu YC, Tsai TJ, Korivi M, Liu JY, Chen HJ, Lin CM, Shen YC, Yang HL (2017) Antitumor properties of Coenzyme Q0 against human ovarian carcinoma cells via induction of ROS-mediated apoptosis and cytoprotective autophagy. Sci Rep 7:1–21. https://doi.org/10.1038/s41598-017-08659-7

    Article  CAS  Google Scholar 

  7. Yun CW, Lee SH (2018) The roles of autophagy in cancer. Int J Mol Sci 19:3466. https://doi.org/10.3390/ijms19113466

    Article  CAS  PubMed Central  Google Scholar 

  8. Shaid S, Brandts CH, Serve H, Dikic I (2013) Ubiquitination and selective autophagy. Cell Death Differ 20:21–30. https://doi.org/10.1038/cdd.2012.72

    Article  CAS  PubMed  Google Scholar 

  9. Vessoni AT, Filippi-Chiela EC, Menck CFM, Lenz G (2013) Autophagy and genomic integrity. Cell Death Differ 20:1444–1454. https://doi.org/10.1038/cdd.2013.103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hamasaki M, Furuta N, Matsuda A, Nezu A, Yamamoto A, Fujita N, Oomori H, Noda T, Haraguchi T, Hiraoka Y, Amano A, Yoshimori T (2013) Autophagosomes form at ER-mitochondria contact sites. Nature 495:389–393. https://doi.org/10.1038/nature11910

    Article  CAS  PubMed  Google Scholar 

  11. Saxton RA, Sabatini DM (2017) mTOR signaling in growth, metabolism, and disease. Cell 168:960–976. https://doi.org/10.1016/j.cell.2017.02.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dibble CC, Manning BD (2013) Signal integration by mTORC1 coordinates nutrient input with biosynthetic output. Nat Cell Biol 15:555–564. https://doi.org/10.1038/ncb2763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Dossou AS, Basu A (2019) The emerging roles of mTORC1 in macromanaging autophagy. Cancers (Basel) 11:1422. https://doi.org/10.3390/cancers11101422

    Article  CAS  Google Scholar 

  14. Xiang H, Zhang J, Lin C, Zhang L, Liu B, Ouyang L (2020) Targeting autophagy-related protein kinases for potential therapeutic purpose. Acta Pharm Sin B 10:569–581. https://doi.org/10.1016/j.apsb.2019.10.003

    Article  CAS  PubMed  Google Scholar 

  15. Mochida K, Oikawa Y, Kimura Y, Kirisako H, Hirano H, Ohsumi Y, Nakatogawa H (2015) Receptor-mediated selective autophagy degrades the endoplasmic reticulum and the nucleus. Nature 522:359–362. https://doi.org/10.1038/nature14506

    Article  CAS  PubMed  Google Scholar 

  16. Lőrincz P, Juhász G (2020) Autophagosome-lysosome fusion. J Mol Biol 432:2462–2482. https://doi.org/10.1016/j.jmb.2019.10.028

    Article  CAS  PubMed  Google Scholar 

  17. Singh SS, Vats S, Chia AY, Zea T, Shuo T, Mei D, Ong S, Arfuso F, Yap CT, Cher B, Sethi G, Huang RY, Shen HM, Manjithaya R, Prem A (2018) Dual role of autophagy in hallmarks of cancer. Oncogene 37:1142–1158. https://doi.org/10.1038/s41388-017-0046-6

    Article  CAS  PubMed  Google Scholar 

  18. Yun CW, Lee SH (2018) The roles of autophagy in cancer. Int J Mol Sci. https://doi.org/10.3390/ijms19113466

    Article  PubMed  PubMed Central  Google Scholar 

  19. Udristioiu A, Nica-Badea D (2019) Autophagy dysfunctions associated with cancer cells and their therapeutic implications. Biomed Pharmacother 115:108892. https://doi.org/10.1016/j.biopha.2019.108892

    Article  CAS  PubMed  Google Scholar 

  20. Fu Y, Huang Z, Hong L, Lu J, Feng D (2019) Targeting ATG4 in cancer therapy. Cancers (Basel) 11:1–17

    Google Scholar 

  21. Aquila S, Santoro M, Caputo A, Panno ML, Pezzi V, De Amicis F (2020) The tumor suppressor PTEN as molecular switch node regulating cell metabolism and autophagy: implications in immune system and tumor microenvironment. Cells 9:1725. https://doi.org/10.3390/cells9071725

    Article  CAS  PubMed Central  Google Scholar 

  22. Jin X, Dai L, Ma Y, Wang J, Liu Z (2020) Implications of HIF-1α in the tumorigenesis and progression of pancreatic cancer. Cancer Cell Int 20:273. https://doi.org/10.1186/s12935-020-01370-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhou J, Li C, Yao W, Alsiddig MC, Huo L, Liu H, Miao YL (2018) Hypoxia-inducible factor-1α-dependent autophagy plays a role in glycolysis switch in mouse granulosa cells. Biol Reprod 99:308–318. https://doi.org/10.1093/biolre/ioy061

    Article  PubMed  Google Scholar 

  24. Marinković M, Šprung M, Novak I (2020) Dimerization of mitophagy receptor BNIP3L/NIX is essential for recruitment of autophagic machinery. Autophagy. https://doi.org/10.1080/15548627.2020.1755120

    Article  PubMed  PubMed Central  Google Scholar 

  25. Daskalaki I, Gkikas I, Tavernarakis N (2018) Hypoxia and selective autophagy in cancer development and therapy. Front Cell Dev Biol 6:1–22. https://doi.org/10.3389/fcell.2018.00104

    Article  Google Scholar 

  26. Feng S, Zha Z, Wang Z, Yang P, Wu J, Li X, Xu Q, Liu Y (2020) Anticancer activity of oleiferoside B involving autophagy and apoptosis through increasing ROS release in MCF-7 cells and SMMC-7721 cells. Nat Prod Res. https://doi.org/10.1080/14786419.2020.1739039

    Article  PubMed  Google Scholar 

  27. Singh R, Letai A, Sarosiek K (2019) Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nat Rev Mol Cell Biol 20:175–193. https://doi.org/10.1038/s41580-018-0089-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mariño G, Niso-Santano M, Baehrecke EH (2014) Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol 15:81–94. https://doi.org/10.1038/nrm3735.Self-consumption

    Article  PubMed  PubMed Central  Google Scholar 

  29. Peña-Blanco A, García-Sáez AJ (2018) Bax, Bak and beyond—mitochondrial performance in apoptosis. FEBS J 285:416–431. https://doi.org/10.1111/febs.14186

    Article  CAS  PubMed  Google Scholar 

  30. D’Orsi B, Mateyka J, Prehn JHM (2017) Control of mitochondrial physiology and cell death by the Bcl-2 family proteins Bax and Bok. Neurochem Int 109:162–170. https://doi.org/10.1016/j.neuint.2017.03.010

    Article  CAS  PubMed  Google Scholar 

  31. Füllsack S, Rosenthal A, Wajant H, Siegmund D (2019) Redundant and receptor-specific activities of TRADD, RIPK1 and FADD in death receptor signaling. Cell Death Dis 10:122. https://doi.org/10.1038/s41419-019-1396-5

    Article  PubMed  PubMed Central  Google Scholar 

  32. Carneiro BA, El-Deiry WS (2020) Targeting apoptosis in cancer therapy. Nat Rev Clin Oncol 17:395–417. https://doi.org/10.1038/s41571-020-0341-y

    Article  PubMed  PubMed Central  Google Scholar 

  33. Tse C, Shoemaker AR, Adickes J, Anderson MG, Chen J, Jin S, Johnson EF, Marsh KC, Mitten MJ, Nimmer P, Roberts L, Tahir SK, Xiao Y, Yang X, Zhang H, Fesik S, Rosenberg SH, Elmore SW (2008) ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res 68:3421–3428. https://doi.org/10.1158/0008-5472.CAN-07-5836

    Article  CAS  PubMed  Google Scholar 

  34. Roberts AW, Seymour JF, Brown JR, Wierda WG, Kipps TJ, Khaw SL, Carney DA, He SZ, Huang DCS, Xiong H, Cui Y, Busman TA, McKeegan EM, Krivoshik AP, Enschede SH, Humerickhouse R (2012) Substantial susceptibility of chronic lymphocytic leukemia to BCL2 inhibition: results of a phase I study of navitoclax in patients with relapsed or refractory disease. J Clin Oncol Off J Am Soc Clin Oncol 30:488–496. https://doi.org/10.1200/JCO.2011.34.7898

    Article  CAS  Google Scholar 

  35. Kipps TJ, Eradat H, Grosicki S, Catalano J, Cosolo W, Dyagil IS, Yalamanchili S, Chai A, Sahasranaman S, Punnoose E, Hurst D, Pylypenko H (2015) A phase 2 study of the BH3 mimetic BCL2 inhibitor navitoclax (ABT-263) with or without rituximab, in previously untreated B-cell chronic lymphocytic leukemia. Leuk Lymphoma 56:2826–2833. https://doi.org/10.3109/10428194.2015.1030638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Lakhani NJ, Rasco DW, Tolcher AW, Huang Y, Ji J, Wang H, Dong Q, Men L, O’Rourke TJ, Chandana SR, Amaya A, Cole Y, Kaiser B, Mays TA, Patnaik A, Papadopoulos KP, Yang D, Zhai Y (2018) A phase I study of novel dual Bcl-2/Bcl-xL inhibitor APG-1252 in patients with advanced small cell lung cancer (SCLC) or other solid tumor. J Clin Oncol 36:2594. https://doi.org/10.1200/JCO.2018.36.15_suppl.2594

    Article  Google Scholar 

  37. Reis B, Jukofsky L, Chen G, Martinelli G, Zhong H, So WV, Dickinson MJ, Drummond M, Assouline S, Hashemyan M, Theron M, Blotner S, Lee J-H, Kasner M, Yoon S-S, Rueger R, Seiter K, Middleton SA, Kelly KR, Vey N, Yee K, Nichols G, Chen L-C, Pierceall WE (2016) Acute myeloid leukemia patients’ clinical response to idasanutlin (RG7388) is associated with pre-treatment MDM2 protein expression in leukemic blasts. Haematologica 101:e185–e188. https://doi.org/10.3324/haematol.2015.139717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Blotner S, Chen L-C, Ferlini C, Zhi J (2018) Phase 1 summary of plasma concentration-QTc analysis for idasanutlin, an MDM2 antagonist, in patients with advanced solid tumors and AML. Cancer Chemother Pharmacol 81:597–607. https://doi.org/10.1007/s00280-018-3534-7

    Article  CAS  PubMed  Google Scholar 

  39. Skalniak L, Kocik J, Polak J, Skalniak A, Rak M, Wolnicka-Glubisz A, Holak TA (2018) Prolonged idasanutlin (RG7388) treatment leads to the generation of p53-mutated cells. Cancers (Basel). https://doi.org/10.3390/cancers10110396

    Article  PubMed Central  Google Scholar 

  40. Tolcher AW, Fang DD, Li Y, Tang Y, Ji J, Wang H, Karim R, Rosas C, Huang Y, Zhai Y (2019) A phase Ib/II study of APG-115 in combination with pembrolizumab in patients with unresectable or metastatic melanomas or advanced solid tumors. Ann Oncol 30:i2. https://doi.org/10.1093/annonc/mdz027

    Article  Google Scholar 

  41. Aguilar A, Lu J, Liu L, Du D, Bernard D, McEachern D, Przybranowski S, Li X, Luo R, Wen B, Sun D, Wang H, Wen J, Wang G, Zhai Y, Guo M, Yang D, Wang S (2017) Discovery of 4-((3’R,4’S,5’R)-6″-Chloro-4’-(3-chloro-2-fluorophenyl)-1’-ethyl-2″-oxodispiro[cyclohexane-1,2’-pyrrolidine-3’,3″-indoline]-5’-carboxamido)bicyclo[2.2.2]octane-1-carboxylic Acid (AA-115/APG-115): a potent and orally active murine double minu. J Med Chem 60:2819–2839. https://doi.org/10.1021/acs.jmedchem.6b01665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Shustov A, Horwitz S, Zain J, Patel M, Sokol L, Meric-Bernstam F, Shapiro G, Nasta S, Janakiram M, Weinstock D, Korn R, Payton M, Annis D, Pinchasik D, Aivado M, Mehta A (2018) Preliminary results of the stapled peptide ALRN-6924, a dual inhibitor of MDMX and MDM2, in two phase IIa dose expansion cohorts in relapsed/refractory TP53 wild-type peripheral T-cell lymphoma. Blood 132:1623. https://doi.org/10.1182/blood-2018-99-116780

    Article  Google Scholar 

  43. Arnhold V, Schmelz K, Proba J, Winkler A, Wünschel J, Toedling J, Deubzer HE, Künkele A, Eggert A, Schulte JH, Hundsdoerfer P (2018) Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma. Oncotarget 9:2304–2319. https://doi.org/10.18632/oncotarget.23409

    Article  PubMed  Google Scholar 

  44. Erba HP, Becker PS, Shami PJ, Grunwald MR, Flesher DL, Zhu M, Rasmussen E, Henary HA, Anderson AA, Wang ES (2019) Phase 1b study of the MDM2 inhibitor AMG 232 with or without trametinib in relapsed/refractory acute myeloid leukemia. Blood Adv 3:1939–1949. https://doi.org/10.1182/bloodadvances.2019030916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cornillie J, Wozniak A, Li H, Gebreyohannes YK, Wellens J, Hompes D, Debiec-Rychter M, Sciot R, Schöffski P (2020) Anti-tumor activity of the MDM2-TP53 inhibitor BI-907828 in dedifferentiated liposarcoma patient-derived xenograft models harboring MDM2 amplification. Clin Transl Oncol Off Publ Fed Spanish Oncol Soc Natl Cancer Inst Mex 22:546–554. https://doi.org/10.1007/s12094-019-02158-z

    Article  CAS  Google Scholar 

  46. Infante JR, Dees EC, Olszanski AJ, Dhuria SV, Sen S, Cameron S, Cohen RB (2014) Phase I dose-escalation study of LCL161, an oral inhibitor of apoptosis proteins inhibitor, in patients with advanced solid tumors. J Clin Oncol Off J Am Soc Clin Oncol 32:3103–3110. https://doi.org/10.1200/JCO.2013.52.3993

    Article  CAS  Google Scholar 

  47. Bardia A, Parton M, Kümmel S, Estévez LG, Huang C-S, Cortés J, Ruiz-Borrego M, Telli ML, Martin-Martorell P, López R, Beck JT, Ismail-Khan R, Chen S-C, Hurvitz SA, Mayer IA, Carreon D, Cameron S, Liao S, Baselga J, Kim S-B (2018) Paclitaxel with inhibitor of apoptosis antagonist, LCL161, for localized triple-negative breast cancer, prospectively stratified by gene signature in a biomarker-driven neoadjuvant trial. J Clin Oncol Off J Am Soc Clin Oncol. https://doi.org/10.1200/JCO.2017.74.8392

    Article  Google Scholar 

  48. Hsu H-Y, Lin T-Y, Hu C-H, Shu DTF, Lu M-K (2018) Fucoidan upregulates TLR4/CHOP-mediated caspase-3 and PARP activation to enhance cisplatin-induced cytotoxicity in human lung cancer cells. Cancer Lett 432:112–120. https://doi.org/10.1016/j.canlet.2018.05.006

    Article  CAS  PubMed  Google Scholar 

  49. Jin Z, McDonald ER, Dicker DT, El-Deiry WS (2004) Deficient tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor transport to the cell surface in human colon cancer cells selected for resistance to TRAIL-induced apoptosis. J Biol Chem 279:35829–35839. https://doi.org/10.1074/jbc.M405538200

    Article  CAS  PubMed  Google Scholar 

  50. Kalal BS, Upadhya D, Pai VR (2017) Chemotherapy resistance mechanisms in advanced skin cancer. Oncol Rev 11:326. https://doi.org/10.4081/oncol.2017.326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. van Noesel MM, van Bezouw S, Salomons GS, Voûte PA, Pieters R, Baylin SB, Herman JG, Versteeg R (2002) Tumor-specific down-regulation of the tumor necrosis factor-related apoptosis-inducing ligand decoy receptors DcR1 and DcR2 is associated with dense promoter hypermethylation. Cancer Res 62:2157–2161

    PubMed  Google Scholar 

  52. Petak I, Danam RP, Tillman DM, Vernes R, Howell SR (2003) Hypermethylation of the gene promoter and enhancer region can regulate Fas expression and sensitivity in colon carcinoma. Cell Death Differ 10:211–217. https://doi.org/10.1038/sj.cdd.4401132

    Article  CAS  PubMed  Google Scholar 

  53. Kurtova AV, Xiao J, Mo Q, Pazhanisamy S, Krasnow R, Lerner SP, Chen F, Roh TT, Lay E, Ho PL, Chan KS (2015) Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance. Nature 517:209–213. https://doi.org/10.1038/nature14034

    Article  CAS  PubMed  Google Scholar 

  54. Ichim G, Tait SWG (2016) A fate worse than death: apoptosis as an oncogenic process. Nat Rev Cancer 16:539–548. https://doi.org/10.1038/nrc.2016.58

    Article  CAS  PubMed  Google Scholar 

  55. Tardáguila M, Mañes S (2013) CX3CL1 at the crossroad of EGF signals: relevance for the progression of ERBB2(+) breast carcinoma. Oncoimmunology 2:e25669. https://doi.org/10.4161/onci.25669

    Article  PubMed  PubMed Central  Google Scholar 

  56. Tang J, Chen Y, Cui R, Li D, Xiao L, Lin P, Du Y, Sun H, Yu X, Zheng X (2015) Upregulation of fractalkine contributes to the proliferative response of prostate cancer cells to hypoxia via promoting the G1/S phase transition. Mol Med Rep 12:7907–7914. https://doi.org/10.3892/mmr.2015.4438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Arandjelovic S, Ravichandran KS (2015) Phagocytosis of apoptotic cells in homeostasis. Nat Immunol 16:907–917. https://doi.org/10.1038/ni.3253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Noy R, Pollard JW (2014) Tumor-associated macrophages: from mechanisms to therapy. Immunity 41:49–61. https://doi.org/10.1016/j.immuni.2014.06.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Vigano S, Alatzoglou D, Irving M, Ménétrier-Caux C, Caux C, Romero P, Coukos G (2019) Targeting adenosine in cancer immunotherapy to enhance T-cell function. Front Immunol 10:925. https://doi.org/10.3389/fimmu.2019.00925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Oh YT, Sun SY (2021) Regulation of cancer metastasis by trail/death receptor signaling. Biomolecules. https://doi.org/10.3390/biom11040499

    Article  PubMed  PubMed Central  Google Scholar 

  61. Miles MA, Hawkins CJ (2017) Executioner caspases and CAD are essential for mutagenesis induced by TRAIL or vincristine. Cell Death Dis 8:e3062–e3062. https://doi.org/10.1038/cddis.2017.454

    Article  PubMed  PubMed Central  Google Scholar 

  62. Hapach LA, Mosier JA, Wang W, Reinhart-King CA (2019) Engineered models to parse apart the metastatic cascade. NPJ Precis Oncol 3:20. https://doi.org/10.1038/s41698-019-0092-3

    Article  PubMed  PubMed Central  Google Scholar 

  63. Su Z, Yang Z, Xu Y, Chen Y, Yu Q (2015) Apoptosis, autophagy, necroptosis, and cancer metastasis. Mol Cancer 14:1–14. https://doi.org/10.1186/s12943-015-0321-5

    Article  CAS  Google Scholar 

  64. Kim Y-N, Koo KH, Sung JY, Yun U-J, Kim H (2012) Anoikis resistance: an essential prerequisite for tumor metastasis. Int J Cell Biol. https://doi.org/10.1155/2012/306879

    Article  PubMed  PubMed Central  Google Scholar 

  65. Paoli P, Giannoni E, Chiarugi P (2013) Anoikis molecular pathways and its role in cancer progression. Biochim Biophys Acta—Mol Cell Res 1833:3481–3498. https://doi.org/10.1016/j.bbamcr.2013.06.026

    Article  CAS  Google Scholar 

  66. Fofaria NM, Srivastava SK (2015) STAT3 induces anoikis resistance, promotes cell invasion and metastatic potential in pancreatic cancer cells. Carcinogenesis 36:142–150. https://doi.org/10.1093/carcin/bgu233

    Article  CAS  PubMed  Google Scholar 

  67. Mak CSL, Yung MMH, Hui LMN, Leung LL, Liang R, Chen K, Liu SS, Qin Y, Leung THY, Lee K-F, Chan KKL, Ngan HYS, Chan DW (2017) MicroRNA-141 enhances anoikis resistance in metastatic progression of ovarian cancer through targeting KLF12/Sp1/survivin axis. Mol Cancer 16:11. https://doi.org/10.1186/s12943-017-0582-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Li J, Li Q, Huang H, Li Y, Li L, Hou W, You Z (2017) Overexpression of miRNA-221 promotes cell proliferation by targeting the apoptotic protease activating factor-1 and indicates a poor prognosis in ovarian cancer. Int J Oncol 50:1087–1096. https://doi.org/10.3892/ijo.2017.3898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Powell E, Piwnica-Worms D, Piwnica-Worms H (2014) Contribution of p53 to metastasis. Cancer Discov 4:405–414. https://doi.org/10.1158/2159-8290.CD-13-0136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Eelen G, Treps L, Li X, Carmeliet P (2020) Basic and therapeutic aspects of angiogenesis updated. Circ Res 127:310–329. https://doi.org/10.1161/CIRCRESAHA.120.316851

    Article  CAS  PubMed  Google Scholar 

  71. Watson EC, Grant ZL, Coultas L (2017) Endothelial cell apoptosis in angiogenesis and vessel regression. Cell Mol Life Sci 74:4387–4403. https://doi.org/10.1007/s00018-017-2577-y

    Article  CAS  PubMed  Google Scholar 

  72. Dimmeler S, Zeiher AM (2000) Endothelial cell apoptosis in angiogenesis and vessel regression. Circ Res 87:434–439. https://doi.org/10.1161/01.res.87.6.434

    Article  CAS  PubMed  Google Scholar 

  73. Zou L, Liu X, Li J, Li W, Zhang L, Li J, Zhang J (2019) Tetramethylpyrazine enhances the antitumor effect of paclitaxel by inhibiting angiogenesis and inducing apoptosis. Front Pharmacol 10:707. https://doi.org/10.3389/fphar.2019.00707

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Yaacoub K, Pedeux R, Tarte K, Thierry G (2016) Role of the tumor microenvironment in regulating apoptosis and cancer progression. Cancer Lett. https://doi.org/10.1016/j.canlet.2016.05.012

    Article  PubMed  Google Scholar 

  75. Wang M, Zhao J, Zhang L, Wei F, Lian Y, Wu Y, Gong Z, Zhang S, Zhou J, Cao K, Li X, Xiong W, Li G, Zeng Z, Guo C (2017) Role of tumor microenvironment in tumorigenesis. J Cancer 8:761–773. https://doi.org/10.7150/jca.17648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Sarode GS, Sarode SC, Maniyar N, Sharma NK, Patil S (2017) Carcinogenesis-relevant biological events in the pathophysiology of the efferocytosis phenomenon. Oncol Rev 11:343. https://doi.org/10.4081/oncol.2017.343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Shin S-A, Moon SY, Park D, Park JB, Lee CS (2019) Apoptotic cell clearance in the tumor microenvironment: a potential cancer therapeutic target. Arch Pharm Res 42:658–671. https://doi.org/10.1007/s12272-019-01169-2

    Article  CAS  PubMed  Google Scholar 

  78. Park S-Y, Kim I-S (2017) Engulfment signals and the phagocytic machinery for apoptotic cell clearance. Exp Mol Med 49:e331. https://doi.org/10.1038/emm.2017.52

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kumar S, Calianese D, Birge RB (2017) Efferocytosis of dying cells differentially modulate immunological outcomes in tumor microenvironment. Immunol Rev 280:149–164. https://doi.org/10.1111/imr.12587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Gray M, Botelho RJ (2017) Phagocytosis: hungry, hungry cells. Methods Mol Biol 1519:1–16. https://doi.org/10.1007/978-1-4939-6581-6_1

    Article  CAS  PubMed  Google Scholar 

  81. Sharma B, Kanwar SS (2018) Phosphatidylserine: a cancer cell targeting biomarker. Semin Cancer Biol 52:17–25. https://doi.org/10.1016/j.semcancer.2017.08.012

    Article  CAS  PubMed  Google Scholar 

  82. Birge RB, Boeltz S, Kumar S, Carlson J, Wanderley J, Calianese D, Barcinski M, Brekken RA, Huang X, Hutchins JT, Freimark B, Empig C, Mercer J, Schroit AJ, Schett G, Herrmann M (2016) Phosphatidylserine is a global immunosuppressive signal in efferocytosis, infectious disease, and cancer. Cell Death Differ 23:962–978. https://doi.org/10.1038/cdd.2016.11

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Chang W, Fa H, Xiao D, Wang J (2020) Targeting phosphatidylserine for cancer therapy: prospects and challenges. Theranostics 10:9214–9229. https://doi.org/10.7150/thno.45125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Lin Y, Xu J, Lan H (2019) Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications. J Hematol Oncol 12:76. https://doi.org/10.1186/s13045-019-0760-3

    Article  PubMed  PubMed Central  Google Scholar 

  85. Garg AD, Agostinis P (2017) Cell death and immunity in cancer: from danger signals to mimicry of pathogen defense responses. Immunol Rev 280:126–148. https://doi.org/10.1111/imr.12574

    Article  CAS  PubMed  Google Scholar 

  86. Zhu J, Powis de Tenbossche CG, Cané S, Colau D, van Baren N, Lurquin C, Schmitt-Verhulst A-M, Liljeström P, Uyttenhove C, Van den Eynde BJ (2017) Resistance to cancer immunotherapy mediated by apoptosis of tumor-infiltrating lymphocytes. Nat Commun 8:1404. https://doi.org/10.1038/s41467-017-00784-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Zhu J, Petit P-F, Van den Eynde BJ (2019) Apoptosis of tumor-infiltrating T lymphocytes: a new immune checkpoint mechanism. Cancer Immunol Immunother 68:835–847. https://doi.org/10.1007/s00262-018-2269-y

    Article  CAS  PubMed  Google Scholar 

  88. Farhood B, Najafi M, Mortezaee K (2019) CD8(+) cytotoxic T lymphocytes in cancer immunotherapy: a review. J Cell Physiol 234:8509–8521. https://doi.org/10.1002/jcp.27782

    Article  CAS  PubMed  Google Scholar 

  89. Ferris RL, Blumenschein G, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375:1856–1867. https://doi.org/10.1056/NEJMoa1602252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Bellmunt J, de Wit R, Vaughn DJ, Fradet Y, Lee J-L, Fong L, Vogelzang NJ, Climent MA, Petrylak DP, Choueiri TK, Necchi A, Gerritsen W, Gurney H, Quinn DI, Culine S, Sternberg CN, Mai Y, Poehlein CH, Perini RF, Bajorin DF (2017) Pembrolizumab as second-line therapy for advanced urothelial carcinoma. N Engl J Med 376:1015–1026. https://doi.org/10.1056/NEJMoa1613683

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Chung C (2018) Restoring the switch for cancer cell death: targeting the apoptosis signaling pathway. Am J Heal Pharm 75:945–952. https://doi.org/10.2146/ajhp170607

    Article  CAS  Google Scholar 

  92. Saito H, Takaya S, Osaki T, Ikeguchi M (2013) Increased apoptosis and elevated Fas expression in circulating natural killer cells in gastric cancer patients. Gastric Cancer 16:473–479. https://doi.org/10.1007/s10120-012-0210-1

    Article  CAS  PubMed  Google Scholar 

  93. Mohme M, Riethdorf S, Pantel K (2017) Circulating and disseminated tumour cells—mechanisms of immune surveillance and escape. Nat Rev Clin Oncol 14:155–167. https://doi.org/10.1038/nrclinonc.2016.144

    Article  CAS  PubMed  Google Scholar 

  94. Motz GT, Santoro SP, Wang L-P, Garrabrant T, Lastra RR, Hagemann IS, Lal P, Feldman MD, Benencia F, Coukos G (2014) Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors. Nat Med 20:607–615. https://doi.org/10.1038/nm.3541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Wang Y-H, Scadden DT (2015) Harnessing the apoptotic programs in cancer stem-like cells. EMBO Rep 16:1084–1098. https://doi.org/10.15252/embr.201439675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Steinbichler TB, Dudás J, Skvortsov S, Ganswindt U, Riechelmann H, Skvortsova I-I (2018) Therapy resistance mediated by cancer stem cells. Semin Cancer Biol 53:156–167. https://doi.org/10.1016/j.semcancer.2018.11.006

    Article  CAS  PubMed  Google Scholar 

  97. Phi LTH, Sari IN, Yang Y-G, Lee S-H, Jun N, Kim KS, Lee YK, Kwon HY (2018) Cancer stem cells (CSCs) in drug resistance and their therapeutic implications in cancer treatment. Stem Cells Int 2018:5416923. https://doi.org/10.1155/2018/5416923

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Li Y, Wang Z, Ajani JA, Song S (2021) Drug resistance and cancer stem cells. Cell Commun Signal 19:19. https://doi.org/10.1186/s12964-020-00627-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Costello RT, Mallet F, Gaugler B, Sainty D, Arnoulet C, Gastaut JA, Olive D (2000) Human acute myeloid leukemia CD34+/CD38- progenitor cells have decreased sensitivity to chemotherapy and Fas-induced apoptosis, reduced immunogenicity, and impaired dendritic cell transformation capacities. Cancer Res 60:4403–4411

    CAS  PubMed  Google Scholar 

  100. Peitzsch C, Kurth I, Kunz-Schughart L, Baumann M, Dubrovska A (2013) Discovery of the cancer stem cell related determinants of radioresistance. Radiother Oncol 108:378–387. https://doi.org/10.1016/j.radonc.2013.06.003

    Article  PubMed  Google Scholar 

  101. Haga RB, Ridley AJ (2016) Rho GTPases: regulation and roles in cancer cell biology. Small GTPases 7:207–221. https://doi.org/10.1080/21541248.2016.1232583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Green DR, Fitzgerald P (2016) Just so stories about the evolution of apoptosis. Curr Biol 26:R620–R627. https://doi.org/10.1016/j.cub.2016.05.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Yang J, Chai X-Q, Zhao X-X, Li X (2017) Comparative genomics revealed the origin and evolution of autophagy pathway. J Syst Evol 55:71–82. https://doi.org/10.1111/jse.12212

    Article  Google Scholar 

  104. Mariño G, Niso-Santano M, Baehrecke EH, Kroemer G (2014) Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol 15:81–94. https://doi.org/10.1038/nrm3735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Germain M, Mathai JP, Shore GC (2002) BH-3-only BIK functions at the endoplasmic reticulum to stimulate cytochrome c release from mitochondria*. J Biol Chem 277:18053–18060. https://doi.org/10.1074/jbc.M201235200

    Article  CAS  PubMed  Google Scholar 

  106. Amr S, Heisey C, Zhang M, Xia X-J, Shows KH, Ajlouni K, Pandya A, Satin LS, El-Shanti H, Shiang R (2007) A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am J Hum Genet 81:673–683. https://doi.org/10.1086/520961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Zhu W, Cowie A, Wasfy GW, Penn LZ, Leber B, Andrews DW (1996) Bcl-2 mutants with restricted subcellular location reveal spatially distinct pathways for apoptosis in different cell types. EMBO J 15:4130–4141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Chang NC, Nguyen M, Germain M, Shore GC (2010) Antagonism of Beclin 1-dependent autophagy by BCL-2 at the endoplasmic reticulum requires NAF-1. EMBO J 29:606–618. https://doi.org/10.1038/emboj.2009.369

    Article  CAS  PubMed  Google Scholar 

  109. Baehrecke EH (2005) Autophagy: dual roles in life and death? Nat Rev Mol Cell Biol 6:505–510. https://doi.org/10.1038/nrm1666

    Article  CAS  PubMed  Google Scholar 

  110. Richard DPN, Youle J (2016) Mechanisms of mitophagy. Nat Rev Mol Cell Biol 12:9–14. https://doi.org/10.1038/nrm3028.Mechanisms

    Article  Google Scholar 

  111. Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8:741–752. https://doi.org/10.1038/nrm2239

    Article  CAS  PubMed  Google Scholar 

  112. Sipos F, Firneisz G, Műzes G (2016) Therapeutic aspects of c-MYC signaling in inflammatory and cancerous colonic diseases. World J Gastroenterol 22:7938–7950. https://doi.org/10.3748/wjg.v22.i35.7938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Manié SN, Lebeau J, Chevet E (2014) Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. 3. Orchestrating the unfolded protein response in oncogenesis: an update. Am J Physiol Physiol 307:C901–C907. https://doi.org/10.1152/ajpcell.00292.2014

    Article  CAS  Google Scholar 

  114. Butler DE, Marlein C, Walker HF, Frame FM, Mann VM, Simms MS, Davies BR, Collins AT, Maitland NJ (2017) Inhibition of the PI3K/AKT/mTOR pathway activates autophagy and compensatory Ras/Raf/MEK/ERK signalling in prostate cancer. Oncotarget 8:56698–56713. https://doi.org/10.18632/oncotarget.18082

    Article  PubMed  PubMed Central  Google Scholar 

  115. González-Polo R-A, Boya P, Pauleau A-L, Jalil A, Larochette N, Souquère S, Eskelinen E-L, Pierron G, Saftig P, Kroemer G (2005) The apoptosis/autophagy paradox: autophagic vacuolization before apoptotic death. J Cell Sci 118:3091–3102. https://doi.org/10.1242/jcs.02447

    Article  CAS  PubMed  Google Scholar 

  116. Zhao Z, Xia G, Li N, Su R, Chen X, Zhong L (2018) Autophagy inhibition promotes bevacizumab-induced apoptosis and proliferation inhibition in colorectal cancer cells. J Cancer 9:3407–3416. https://doi.org/10.7150/jca.24201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Das DN, Naik PP, Mukhopadhyay S, Panda PK, Sinha N, Meher BR, Bhutia SK (2017) Elimination of dysfunctional mitochondria through mitophagy suppresses benzo[a]pyrene-induced apoptosis. Free Radic Biol Med 112:452–463. https://doi.org/10.1016/j.freeradbiomed.2017.08.020

    Article  CAS  PubMed  Google Scholar 

  118. Grasso D, Ropolo A, Lo A, Ré V, Boggio MI, Molejón JL, Iovanna CD, Gonzalez R, Urrutia MI, Vaccaro (2011) Zymophagy, a novel selective autophagy pathway mediated by VMP1-USP9x-p62, prevents pancreatic cell death. J Biol Chem 286:8308–8324. https://doi.org/10.1074/jbc.M110.197301

    Article  CAS  PubMed  Google Scholar 

  119. Hou W, Han J, Lu C, Goldstein LA, Rabinowich H (2010) Autophagic degradation of active caspase-8: a crosstalk mechanism between autophagy and apoptosis. Autophagy 6:891–900. https://doi.org/10.4161/auto.6.7.13038

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Pagliarini V, Wirawan E, Romagnoli A, Ciccosanti F, Lisi G, Lippens S, Cecconi F, Fimia GM, Vandenabeele P, Corazzari M, Piacentini M (2012) Autophagic pro-survival response Proteolysis of Ambra1 during apoptosis has a role in the inhibition of the autophagic pro-survival response. Cell Death Differ 19:1495–1504. https://doi.org/10.1038/cdd.2012.27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Lamy L, Ngo VN, Emre NCT, Shaffer AL, Yang Y, Tian E, Nair V, Kruhlak MJ, Zingone A, Landgren O, Staudt LM (2013) Control of autophagic cell death by caspase-10 in multiple myeloma. Cancer Cell 23:435–449. https://doi.org/10.1016/j.ccr.2013.02.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Dong X, Fu J, Yin X, Cao S, Li X, Lin L, Ni J (2016) Emodin: a review of its pharmacology, toxicity and pharmacokinetics: emodin: pharmacology, toxicity and pharmacokinetics. Phyther Res 30:1207–1218. https://doi.org/10.1002/ptr.5631

    Article  CAS  Google Scholar 

  123. Wang Y, Luo Q, He X, Wei H, Wang T, Shao J, Jiang X (2018) Emodin induces apoptosis of colon cancer cells via induction of autophagy in a ROS-dependent manner. Oncol Res 26:889–899. https://doi.org/10.3727/096504017X15009419625178

    Article  PubMed  PubMed Central  Google Scholar 

  124. Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L, Brunner T, Simon HU (2006) Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol 8:1124–1132. https://doi.org/10.1038/ncb1482

    Article  CAS  PubMed  Google Scholar 

  125. Chen H, Zhao C, He R, Zhou M, Liu Y, Guo X, Wang M, Zhu F, Qin R, Li X (2019) Danthron suppresses autophagy and sensitizes pancreatic cancer cells to doxorubicin. Toxicol Vitr 54:345–353. https://doi.org/10.1016/j.tiv.2018.10.019

    Article  CAS  Google Scholar 

  126. Shui L, Wang W, Xie M, Ye B, Li X, Liu Y, Zheng M (2020) Isoquercitrin induces apoptosis and autophagy in hepatocellular carcinoma cells via AMPK/mTOR/p70S6K signaling pathway. Aging (Albany NY) 12:24318–24332. https://doi.org/10.18632/aging.202237

    Article  CAS  Google Scholar 

  127. Young MM, Takahashi Y, Khan O, Park S, Hori T, Yun J, Sharma AK, Amin S, Hu CD, Zhang J, Kester M, Wang HG (2012) Autophagosomal membrane serves as platform for intracellular death-inducing signaling complex (iDISC)-mediated caspase-8 activation and apoptosis. J Biol Chem 287:12455–12468. https://doi.org/10.1074/jbc.M111.309104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Rathore R, McCallum JE, Varghese E, Florea A-M, Büsselberg D (2017) Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs). Apoptosis 22:898–919. https://doi.org/10.1007/s10495-017-1375-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Xie Q, Liu Y, Li X (2020) The interaction mechanism between autophagy and apoptosis in colon cancer. Transl Oncol 13:100871. https://doi.org/10.1016/j.tranon.2020.100871

    Article  PubMed  PubMed Central  Google Scholar 

  130. Zhu J, Zhao L, Luo B, Sheng W (2019) Shikonin regulates invasion and autophagy of cultured colon cancer cells by inhibiting yes–associated protein. Oncol Lett 18:6117–6125. https://doi.org/10.3892/ol.2019.10980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Michaud M, Martins I, Sukkurwala AQ, Adjemian S, Ma Y, Pellegatti P, Shen S, Kepp O, Scoazec M, Mignot G, Rello-Varona S, Tailler M, Menger L, Vacchelli E, Galluzzi L, Ghiringhelli F, di Virgilio F, Zitvogel L, Kroemer G (2011) Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 334:1573–1577. https://doi.org/10.1126/science.1208347

    Article  CAS  PubMed  Google Scholar 

  132. Crighton D, Wilkinson S, O’Prey J, Syed N, Smith P, Harrison PR, Gasco M, Garrone O, Crook T, Ryan KM (2006) DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell 126:121–134. https://doi.org/10.1016/j.cell.2006.05.034

    Article  CAS  PubMed  Google Scholar 

  133. White E (2016) Autophagy and p53. Cold Spring Harb Perspect Med 6:a026120–a026120. https://doi.org/10.1101/cshperspect.a026120

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Li M, Gao P, Zhang J (2016) Crosstalk between autophagy and apoptosis: potential and emerging therapeutic targets for cardiac diseases. Int J Mol Sci 17:332. https://doi.org/10.3390/ijms17030332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Moghtaderi H, Sepehri H, Attari F (2017) Combination of arabinogalactan and curcumin induces apoptosis in breast cancer cells in vitro and inhibits tumor growth via overexpression of p53 level in vivo. Biomed Pharmacother 88:582–594. https://doi.org/10.1016/j.biopha.2017.01.072

    Article  CAS  PubMed  Google Scholar 

  136. De U, Son JY, Sachan R, Park YJ, Kang D, Yoon K, Lee BM, Kim IS, Moon HR, Kim HS (2018) A new synthetic histone deacetylase inhibitor, MHY2256, induces apoptosis and autophagy cell death in endometrial cancer cells via p53 acetylation. Int J Mol Sci 19:2743. https://doi.org/10.3390/ijms19092743

    Article  CAS  PubMed Central  Google Scholar 

  137. Mrakovcic M, Fröhlich LF (2018) p53-mediated molecular control of autophagy in tumor cells. Biomolecules 8:14. https://doi.org/10.3390/biom8020014

    Article  CAS  PubMed Central  Google Scholar 

  138. Lin C-F, Chien S-Y, Chen C-L, Hsieh C-Y, Tseng P-C, Wang Y-C (2016) IFN-γ induces mimic extracellular trap cell death in lung epithelial cells through autophagy-regulated DNA damage. J Interf Cytokine Res 36:100–112. https://doi.org/10.1089/jir.2015.0011

    Article  CAS  Google Scholar 

  139. Pyo JO, Jang MH, Kwon YK, Lee HJ, Il Jun J, Woo HN, Cho DH, Choi BY, Lee H, Kim JH, Mizushima N, Oshumi Y, Jung YK (2005) Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J Biol Chem 280:20722–20729. https://doi.org/10.1074/jbc.M413934200

    Article  CAS  PubMed  Google Scholar 

  140. Ye X, Zhou X-J, Zhang H (2018) Exploring the role of autophagy-related gene 5 (ATG5) yields important insights into autophagy in autoimmune/autoinflammatory diseases. Front Immunol 9:2334. https://doi.org/10.3389/fimmu.2018.02334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Nian H, Ma B (2021) Calpain–calpastatin system and cancer progression. Biol Rev 96:961–975. https://doi.org/10.1111/brv.12686

    Article  PubMed  Google Scholar 

  142. Zhang J, Zhang S, Shi Q, Allen TD, You F, Yang D (2020) The anti-apoptotic proteins Bcl-2 and Bcl-xL suppress Beclin 1/Atg6-mediated lethal autophagy in polyploid cells, Exp. Cell Res 394:112112. https://doi.org/10.1016/j.yexcr.2020.112112

    Article  CAS  Google Scholar 

  143. Gordy C, He YW (2012) The crosstalk between autophagy and apoptosis: where does this lead? Protein Cell 3:17–27. https://doi.org/10.1007/s13238-011-1127-x

    Article  PubMed  PubMed Central  Google Scholar 

  144. Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J, Pedraza-Chaverri J (2014) The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal 26:2694–2701. https://doi.org/10.1016/j.cellsig.2014.08.019

    Article  CAS  PubMed  Google Scholar 

  145. Xie W, Wulin H, Shao G, Wei L, Qi R, Ma B, Chen N, Shi R (2020) Polygalasaponin F inhibits neuronal apoptosis induced by oxygen-glucose deprivation and reoxygenation through the PI3K/Akt pathway. Basic Clin Pharmacol Toxicol 127:196–204. https://doi.org/10.1111/bcpt.13408

    Article  CAS  PubMed  Google Scholar 

  146. Safa AR (2013) Roles of c-FLIP in apoptosis, necroptosis, and autophagy. J Carcinog Mutagen. https://doi.org/10.4172/2157-2518.S6-003.Roles

    Article  PubMed  PubMed Central  Google Scholar 

  147. Singh P, Ravanan P, Talwar P (2016) Death associated protein kinase 1 (DAPK1): a regulator of apoptosis and autophagy. Front Mol Neurosci 9:46. https://doi.org/10.3389/fnmol.2016.00046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Elbadawy M, Usui T, Yamawaki H, Sasaki K (2018) Novel functions of death-associated protein kinases through mitogen-activated protein kinase-related signals. Int J Mol Sci 19:3031. https://doi.org/10.3390/ijms19103031

    Article  CAS  PubMed Central  Google Scholar 

  149. Yu L, Wan F, Dutta S, Welsh S, Liu ZH, Freundt E, Baehrecke EH, Lenardo M (2006) Autophagic programmed cell death by selective catalase degradation. Proc Natl Acad Sci USA 103:4952–4957. https://doi.org/10.1073/pnas.0511288103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Bonapace L, Bornhauser BC, Schmitz M, Cario G, Ziegler U, Niggli FK, Schäfer BW, Schrappe M, Stanulla M, Bourquin JP (2010) Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance. J Clin Invest 120:1310–1323. https://doi.org/10.1172/JCI39987

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Yao Z, Zhang P, Guo H, Shi J, Liu S, Liu Y, Zheng D (2015) RIP1 modulates death receptor mediated apoptosis and autophagy in macrophages. Mol Oncol 9:806–817. https://doi.org/10.1016/j.molonc.2014.12.004

    Article  CAS  PubMed  Google Scholar 

  152. Verzella D, Pescatore A, Capece D, Vecchiotti D, Ursini MV, Franzoso G, Alesse E, Zazzeroni F (2020) Life, death, and autophagy in cancer: NF-κB turns up everywhere. Cell Death Dis 11:210. https://doi.org/10.1038/s41419-020-2399-y

    Article  PubMed  PubMed Central  Google Scholar 

  153. Blaser H, Dostert C, Mak TW, Brenner D (2016) TNF and ROS crosstalk in inflammation. Trends Cell Biol 26:249–261. https://doi.org/10.1016/j.tcb.2015.12.002

    Article  CAS  PubMed  Google Scholar 

  154. Ryan KM, Ernst MK, Rice NR, Vousden KH (2000) Role of NF-κB in p53-mediated programmed cell death. Nature 404:892–897. https://doi.org/10.1038/35009130

    Article  CAS  PubMed  Google Scholar 

  155. Khandelwal N, Simpson J, Taylor G, Rafique S, Whitehouse A, Hiscox J, Stark LA (2011) Nucleolar NF-κB/RelA mediates apoptosis by causing cytoplasmic relocalization of nucleophosmin. Cell Death Differ 18:1889–1903. https://doi.org/10.1038/cdd.2011.79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Kong P, Zhu X, Geng Q, Xia L, Sun X, Chen Y, Li W, Zhou Z, Zhan Y, Xu D (2017) The microRNA-423-3p-Bim axis promotes cancer progression and activates oncogenic autophagy in gastric cancer. Mol Ther 25:1027–1037. https://doi.org/10.1016/j.ymthe.2017.01.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Su B, Wang X-T, Sun Y-H, Long M-Y, Zheng J, Wu W-H, Li L (2020) Ischemia/hypoxia inhibits cardiomyocyte autophagy and promotes apoptosis via the Egr-1/Bim/Beclin-1 pathway. J Geriatr Cardiol 17:284–293. https://doi.org/10.11909/j.issn.1671-5411.2020.05.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Yang D, Okamura H, Teramachi J, Haneji T (2016) Histone demethylase Jmjd3 regulates osteoblast apoptosis through targeting anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bim. Biochim Biophys Acta—Mol Cell Res 1863:650–659. https://doi.org/10.1016/j.bbamcr.2016.01.006

    Article  CAS  Google Scholar 

  159. Menon MB, Dhamija S (2018) Beclin 1 phosphorylation—at the Center of Autophagy Regulation. Front Cell Dev Biol 6:137. https://doi.org/10.3389/fcell.2018.00137

    Article  PubMed  PubMed Central  Google Scholar 

  160. Oral O, Akkoc Y, Bayraktar O, Gozuacik D (2016) Physiological and pathological significance of the molecular cross-talk between autophagy and apoptosis. Histol Histopathol 31:479–498. https://doi.org/10.14670/HH-11-714

    Article  CAS  PubMed  Google Scholar 

  161. Yuan Y, Zhang Y, Han L, Sun S, Shu Y (2018) miR-183 inhibits autophagy and apoptosis in gastric cancer cells by targeting ultraviolet radiation resistance-associated gene. Int J Mol Med 42:3562–3570. https://doi.org/10.3892/ijmm.2018.3871

    Article  CAS  PubMed  Google Scholar 

  162. Murrow L, Malhotra R, Debnath J (2015) ATG12-ATG3 interacts with Alix to promote basal autophagic flux and late endosome function. Nat Cell Biol 17:300–310. https://doi.org/10.1038/ncb3112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Tsai T-C, Lai K-H, Su J-H, Wu Y-J, Sheu J-H (2018) 7-Acetylsinumaximol B induces apoptosis and autophagy in human gastric carcinoma cells through mitochondria dysfunction and activation of the PERK/eIF2α/ATF4/CHOP signaling pathway. Mar Drugs 16:104. https://doi.org/10.3390/md16040104

    Article  CAS  PubMed Central  Google Scholar 

  164. Alway SE (2019) Chap 27—antioxidants and polyphenols mediate mitochondrial mediated muscle death signaling in sarcopenia. Academic Press, Cambridge, pp 439–494. https://doi.org/10.1016/B978-0-12-810422-4.00026-9

    Book  Google Scholar 

  165. Su M, Mei Y, Sinha S (2013) Role of the crosstalk between autophagy and apoptosis in cancer. J Oncol. https://doi.org/10.1155/2013/102735

    Article  PubMed  PubMed Central  Google Scholar 

  166. Fairlie WD, Tran S, Lee EF (2020) Crosstalk between apoptosis and autophagy signaling pathways, 1st edn. Elsevier, Amsterdam. https://doi.org/10.1016/bs.ircmb.2020.01.003

    Book  Google Scholar 

  167. McComb S, Chan PK, Guinot A, Hartmannsdottir H, Jenni S, Dobay MP, Bourquin J-P, Bornhauser BC (2019) Efficient apoptosis requires feedback amplification of upstream apoptotic signals by effector caspase-3 or -7. Sci Adv 5:eaau9433. https://doi.org/10.1126/sciadv.aau9433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Tracking Autophagy With LC3B & p62 - IN, (n.d.). http://www.thermofisher.com/in/en/home/life-science/cell-analysis/cell-viability-and-regulation/autophagy/autophagy-lc3b-p62.html

  169. Ojha R, Ishaq M, Singh S (2015) Caspase-mediated crosstalk between autophagy and apoptosis: mutual adjustment or matter of dominance. J Cancer Res Ther 11:514–524. https://doi.org/10.4103/0973-1482.163695

    Article  CAS  PubMed  Google Scholar 

  170. Tsapras P, Nezis IP (2017) Caspase involvement in autophagy. Cell Death Differ 24:1369–1379. https://doi.org/10.1038/cdd.2017.43

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Young MM, Takahashi Y, Khan O, Park S, Hori T, Yun J, Sharma AK, Amin S, Hu C-D, Zhang J, Kester M, Wang H-G (2012) Autophagosomal membrane serves as platform for intracellular death-inducing signaling complex (iDISC)-mediated caspase-8 activation and apoptosis. J Biol Chem 287:12455–12468. https://doi.org/10.1074/jbc.M111.309104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Liu T, Zhang J, Li K, Deng L, Wang H (2020) Combination of an autophagy inducer and an autophagy inhibitor: a smarter strategy emerging in cancer therapy. Front Pharmacol 11:408. https://doi.org/10.3389/fphar.2020.00408

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Fitzwalter BE, Towers CG, Sullivan KD, Andrysik Z, Hoh M, Ludwig M, O’Prey J, Ryan KM, Espinosa JM, Morgan MJ, Thorburn A (2018) Autophagy inhibition mediates apoptosis sensitization in cancer therapy by relieving FOXO3a turnover. Dev Cell 44:555–565.e3. https://doi.org/10.1016/j.devcel.2018.02.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Chen M-C, Lin Y-C, Liao Y-H, Liou J-P, Chen C-H (2019) MPT0G612, a novel HDAC6 inhibitor, induces apoptosis and suppresses IFN-γ-induced programmed death-ligand 1 in human colorectal carcinoma cells. Cancers (Basel) 11:1617. https://doi.org/10.3390/cancers11101617

    Article  CAS  Google Scholar 

  175. Yu H, Wu C-L, Wang X, Ban Q, Quan C, Liu M, Dong H, Li J, Kim G-Y, Choi YH, Wang Z, Jin C-Y (2019) SP600125 enhances C-2-induced cell death by the switch from autophagy to apoptosis in bladder cancer cells. J Exp Clin Cancer Res 38:448. https://doi.org/10.1186/s13046-019-1467-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Tilija Pun N, Jang W-J, Jeong C-H (2020) Role of autophagy in regulation of cancer cell death/apoptosis during anti-cancer therapy: focus on autophagy flux blockade. Arch Pharm Res 43:475–488. https://doi.org/10.1007/s12272-020-01239-w

    Article  CAS  PubMed  Google Scholar 

  177. Peng Y, Qiu L, Xu D, Zhang L, Yu H, Ding Y, Deng L, Lin J (2017) M4IDP, a zoledronic acid derivative, induces G1 arrest, apoptosis and autophagy in HCT116 colon carcinoma cells via blocking PI3K/Akt/mTOR pathway. Life Sci 185:63–72. https://doi.org/10.1016/j.lfs.2017.07.024

    Article  CAS  PubMed  Google Scholar 

  178. Kaluzki I, Hailemariam-Jahn T, Doll M, Kaufmann R, Balermpas P, Zöller N, Kippenberger S, Meissner M (2019) Dimethylfumarate inhibits colorectal carcinoma cell proliferation: evidence for cell cycle arrest, apoptosis and autophagy. Cells 8:1329. https://doi.org/10.3390/cells8111329

    Article  CAS  PubMed Central  Google Scholar 

  179. Gugnoni M, Sancisi V, Manzotti G, Gandolfi G, Ciarrocchi A (2016) Autophagy and epithelial–mesenchymal transition: an intricate interplay in cancer. Cell Death Dis 7:e2520–e2520. https://doi.org/10.1038/cddis.2016.415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Dang S, Yu Z, Zhang C, Zheng J, Li K, Wu Y, Qian L, Yang Z, Li X, Zhang Y, Wang R (2015) Autophagy promotes apoptosis of mesenchymal stem cells under inflammatory microenvironment. Stem Cell Res Ther 6:247. https://doi.org/10.1186/s13287-015-0245-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Lin Y, Jiang D, Li Y, Han X, Yu D, Park JH, Jin Y-H (2015) Effect of sun ginseng potentiation on epirubicin and paclitaxel-induced apoptosis in human cervical cancer cells. J Ginseng Res 39:22–28. https://doi.org/10.1016/j.jgr.2014.08.001

    Article  PubMed  Google Scholar 

  182. Hong X, Li S, Li W, Xie M, Wei Z, Guo H, Wei W, Zhang S (2019) Disruption of protein neddylation with MLN4924 attenuates paclitaxel-induced apoptosis and microtubule polymerization in ovarian cancer cells. Biochem Biophys Res Commun 508:986–990. https://doi.org/10.1016/j.bbrc.2018.12.048

    Article  CAS  PubMed  Google Scholar 

  183. Deng L, Wu X, Zhu X, Yu Z, Liu Z, Wang J, Zheng Y (2021) Combination effect of curcumin with docetaxel on the PI3K/AKT/mTOR pathway to induce autophagy and apoptosis in esophageal squamous cell carcinoma. Am J Transl Res 13:57–72

    CAS  PubMed  PubMed Central  Google Scholar 

  184. Zhao P, Li M, Wang Y, Chen Y, He C, Zhang X, Yang T, Lu Y, You J, Lee RJ, Xiang G (2018) Enhancing anti-tumor efficiency in hepatocellular carcinoma through the autophagy inhibition by miR-375/sorafenib in lipid-coated calcium carbonate nanoparticles. Acta Biomater 72:248–255. https://doi.org/10.1016/j.actbio.2018.03.022

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to BITS-Pilani, Pilani campus for providing research-initiation grant (RIG) and stipend to the student for carrying out the literature search.

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Authors and Affiliations

  1. Department of Pharmacy, Birla Institute of Technology and Sciences (BITS), Pilani Campus, Pilani, Rajasthan, 333031, India

    Shreya Das & Richa Shrivastava

  2. Department of Pathology, Case Western Reserve University, Cleveland, OH, USA

    Nidhi Shukla

  3. Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA

    Shashi Shekhar Singh

  4. Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, 226025, India

    Sapana Kushwaha

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Das, S., Shukla, N., Singh, S.S. et al. Mechanism of interaction between autophagy and apoptosis in cancer. Apoptosis 26, 512–533 (2021). https://doi.org/10.1007/s10495-021-01687-9

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