[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

MZF1 mediates oncogene-induced senescence by promoting the transcription of p16INK4A

Oncogene volume 41, pages 414–426 (2022)Cite this article

Subjects

A Correction to this article was published on 29 November 2024

This article has been updated

Abstract

Oncogene induced senescence is a tumor suppressing defense mechanism, in which the cell cycle-dependent protein kinase (CDK) inhibitor p16INK4A (encoded by the CDKN2A gene) plays a key role. We previously reported that a transcriptional co-activator chromodomain helicase DNA binding protein 7 (CHD7) mediates oncogenic ras-induced senescence by inducing transcription of the p16INK4A gene. In the current study, we identified myeloid zinc finger 1 (MZF1) as the transcriptional factor that recruits CHD7 to the p16INK4A promoter, where it mediates oncogenic ras-induced p16INK4A transcription and senescence through CHD7, in primary human cells from multiple origins. Moreover, the expression of MZF1 is induced by oncogenic ras in senescent cells through the c-Jun and Ets1 transcriptional factors upon their activation by the Ras-Raf-1-MEK-ERK signaling pathway. In non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma (PAAD) where activating ras mutations occur frequently, reduced MZF1 expression is observed in tumors, as compared to corresponding normal tissues, and correlates with poor patient survival. Analysis of single cell RNA-sequencing data from PAAD patients revealed that among the tumor cells with normal RB expression levels, those with reduced levels of MZF1 are more likely to express lower p16INK4A levels. These findings have identified novel signaling components in the pathway that mediates induction of the p16INK4A tumor suppressor and the senescence response, and suggested that MZF1 is a potential tumor suppressor in at least some cancer types, the loss of which contributes to the inactivation of the p16INK4A/RB pathway and disruption of senescence in tumor cells with intact RB.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: MZF1 mediates oncogenic ras-induced recruitment of CHD7 to the p16INK4A promoter and CHD7-stimulated p16INK4A transcription.
Fig. 2: The long MZF1 isoform mediates oncogenic ras-induced p16INK4A transcription.
Fig. 3: MZF1 mediates oncogenic ras-induced senescence through CHD7.
Fig. 4: Oncogenic ras induces MZF1 expression through the Raf1-MEK1-ERK pathway.
Fig. 5: Oncogenic ras-induced MZF1 transcription requires c-Jun and Ets1.
Fig. 6: The c-Jun and Ets1 binding sites on the MZF1 promoter are required for oncogenic ras-induced MZF1 transcription.
Fig. 7: Reduced MZF1 expression in tumors correlates with poor patient survival in NSCLC and PAAD.
Fig. 8: Analysis of single cell RNA-seq data reveals a correlation between low MZF1 expression and reduced CDKN2A/p16INK4A expression in PAAD.

Similar content being viewed by others

Change history

  • 29 November 2024

    The original online version of this article was revised. Following the publication of this article, an error was noted in the Western blotting panel for Ets1 in Figure 5C. The image from a longer exposure of the MZF1-L blot processed in parallel was used for Ets1 by an inadvertent mistake. The authors have now replaced the Ets1 panel with the corrected image.

    A further error was noted in the Western blotting panel for MZF1-L/S in Figure S4A. The image for the MZF1-L/S blot presented in Figure 2C from another batch of cell lysates was inadvertently used. The authors have now replaced the MZF1-L/S panel with the correct image.

  • 29 November 2024

    A Correction to this paper has been published: https://doi.org/10.1038/s41388-024-03229-4

References

  1. Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C, et al. Cellular senescence: defining a path forward. Cell. 2019;179:813–27.

    Article  CAS  PubMed  Google Scholar 

  2. Krizhanovsky V, Xue W, Zender L, Yon M, Hernando E, Lowe SW. Implications of cellular senescence in tissue damage response, tumor suppression, and stem cell biology. Cold Spring Harb Symp Quant Biol. 2008;73:513–22.

    Article  CAS  PubMed  Google Scholar 

  3. Lee S, Lee JS. Cellular senescence: a promising strategy for cancer therapy. BMB Rep. 2019;52:35–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lee S, Schmitt CA. The dynamic nature of senescence in cancer. Nat Cell Biol. 2019;21:94–101.

    Article  CAS  PubMed  Google Scholar 

  5. Zhu J, Woods D, McMahon M, Bishop JM. Senescence of human fibroblasts induced by oncogenic Raf. Genes Dev. 1998;12:2997–3007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ferbeyre G, de Stanchina E, Lin AW, Querido E, McCurrach ME, Hannon GJ, et al. Oncogenic ras and p53 cooperate to induce cellular senescence. Mol Cell Biol. 2002;22:3497–508.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sato M, Vaughan MB, Girard L, Peyton M, Lee W, Shames DS, et al. Multiple oncogenic changes (K-RAS(V12), p53 knockdown, mutant EGFRs, p16 bypass, telomerase) are not sufficient to confer a full malignant phenotype on human bronchial epithelial cells. Cancer Res. 2006;66:2116–28.

    Article  CAS  PubMed  Google Scholar 

  8. Iwasaki O, Tanizawa H, Kim KD, Kossenkov A, Nacarelli T, Tashiro S, et al. Involvement of condensin in cellular senescence through gene regulation and compartmental reorganization. Nat Commun. 2019;10:5688.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hernandez-Segura A, de Jong TV, Melov S, Guryev V, Campisi J, Demaria M. Unmasking transcriptional heterogeneity in senescent cells. Curr Biol. 2017;27:2652–2660 e2654.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Collado M, Serrano M. Senescence in tumours: evidence from mice and humans. Nat Rev Cancer. 2010;10:51–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. di Magliano MP, Logsdon CD. Roles for KRAS in pancreatic tumor development and progression. Gastroenterology. 2013;144:1220–9.

    Article  PubMed  Google Scholar 

  12. Courtois-Cox S, Jones SL, Cichowski K. Many roads lead to oncogene-induced senescence. Oncogene. 2008;27:2801–9.

    Article  CAS  PubMed  Google Scholar 

  13. Hellmich C, Moore JA, Bowles KM, Rushworth SA. Bone marrow senescence and the microenvironment of hematological malignancies. Front Oncol. 2020;10:230.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Liu XL, Ding J, Meng LH. Oncogene-induced senescence: a double edged sword in cancer. Acta Pharm Sin. 2018;39:1553–8.

    Article  CAS  Google Scholar 

  15. Ohtani N, Takahashi A, Mann DJ, Hara E. Cellular senescence: a double-edged sword in the fight against cancer. Exp Dermatol. 2012;21:1–4. Suppl 1

    Article  CAS  PubMed  Google Scholar 

  16. Schosserer M, Grillari J, Breitenbach M. The dual role of cellular senescence in developing tumors and their response to cancer therapy. Front Oncol. 2017;7:278.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Peterson MJ, Morris JF. Human myeloid zinc finger gene MZF produces multiple transcripts and encodes a SCAN box protein. Gene. 2000;254:105–18.

    Article  CAS  PubMed  Google Scholar 

  18. Murai K, Murakami H, Nagata S. A novel form of the myeloid-specific zinc finger protein (MZF-2). Genes Cells. 1997;2:581–91.

    Article  CAS  PubMed  Google Scholar 

  19. Eguchi T, Prince T, Wegiel B, Calderwood SK. Role and regulation of myeloid zinc finger protein 1 in cancer. J Cell Biochem. 2015;116:2146–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Brix DM, Bundgaard Clemmensen KK, Kallunki T. Zinc finger transcription factor MZF1-A specific regulator of cancer invasion. Cells. 2020;9:223.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Gaboli M, Kotsi PA, Gurrieri C, Cattoretti G, Ronchetti S, Cordon-Cardo C, et al. Mzf1 controls cell proliferation and tumorigenesis. Genes Dev. 2001;15:1625–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hsieh YH, Wu TT, Tsai JH, Huang CY, Hsieh YS, Liu JY. PKCalpha expression regulated by Elk-1 and MZF-1 in human HCC cells. Biochem Biophys Res Commun. 2006;339:217–25.

    Article  CAS  PubMed  Google Scholar 

  23. Liu X, Lei Q, Yu Z, Xu G, Tang H, Wang W, et al. MiR-101 reverses the hypomethylation of the LMO3 promoter in glioma cells. Oncotarget. 2015;6:7930–43.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Tsai LH, Wu JY, Cheng YW, Chen CY, Sheu GT, Wu TC, et al. The MZF1/c-MYC axis mediates lung adenocarcinoma progression caused by wild-type lkb1 loss. Oncogene. 2015;34:1641–9.

    Article  CAS  PubMed  Google Scholar 

  25. Eguchi T, Prince TL, Tran MT, Sogawa C, Lang BJ. Calderwood SKMZF1 and SCAND1 reciprocally regulate CDC37 gene expression in prostate cancer. Cancers (Basel). 2019;11:792.

    Article  PubMed  Google Scholar 

  26. Hsieh YH, Wu TT, Huang CY, Hsieh YS, Liu JY. Suppression of tumorigenicity of human hepatocellular carcinoma cells by antisense oligonucleotide MZF-1. Chin J Physiol. 2007;50:9–15.

    CAS  PubMed  Google Scholar 

  27. Rafn B, Nielsen CF, Andersen SH, Szyniarowski P, Corcelle-Termeau E, Valo E, et al. ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression. Mol Cell. 2012;45:764–76.

    Article  CAS  PubMed  Google Scholar 

  28. Tsai SJ, Hwang JM, Hsieh SC, Ying TH, Hsieh YH. Overexpression of myeloid zinc finger 1 suppresses matrix metalloproteinase-2 expression and reduces invasiveness of SiHa human cervical cancer cells. Biochem Biophys Res Commun. 2012;425:462–7.

    Article  CAS  PubMed  Google Scholar 

  29. Deng Y, Wang J, Wang G, Jin Y, Luo X, Xia X, et al. p55PIK transcriptionally activated by MZF1 promotes colorectal cancer cell proliferation. Biomed Res Int. 2013;2013:868131.

    Article  PubMed  Google Scholar 

  30. Lee JH, Kim SS, Lee HS, Hong S, Rajasekaran N, Wang LH, et al. Upregulation of SMAD4 by MZF1 inhibits migration of human gastric cancer cells. Int J Oncol. 2017;50:272–82.

    Article  PubMed  Google Scholar 

  31. Li GQ, He Q, Yang L, Wang SB, Yu DD, He YQ, et al. Clinical significance of myeloid zinc finger 1 expression in the progression of gastric tumourigenesis. Cell Physiol Biochem. 2017;44:1242–50.

    Article  CAS  PubMed  Google Scholar 

  32. Su W, Hong L, Xu X, Huang S, Herpai D, Li L, et al. miR-30 disrupts senescence and promotes cancer by targeting both p16(INK4A) and DNA damage pathways. Oncogene. 2018;37:5618–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Feng W, Shao C, Liu HK. Versatile roles of the chromatin remodeler CHD7 during brain development and disease. Front Mol Neurosci. 2017;10:309.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Feng W, Khan MA, Bellvis P, Zhu Z, Bernhardt O, Herold-Mende C, et al. The chromatin remodeler CHD7 regulates adult neurogenesis via activation of SoxC transcription factors. Cell Stem Cell. 2013;13:62–72.

    Article  CAS  PubMed  Google Scholar 

  35. Bajpai R, Chen DA, Rada-Iglesias A, Zhang J, Xiong Y, Helms J, et al. CHD7 cooperates with PBAF to control multipotent neural crest formation. Nature. 2010;463:958–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Schnetz MP, Handoko L, Akhtar-Zaidi B, Bartels CF, Pereira CF, Fisher AG, et al. CHD7 targets active gene enhancer elements to modulate ES cell-specific gene expression. PLoS Genet. 2010;6:e1001023.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Engelen E, Akinci U, Bryne JC, Hou J, Gontan C, Moen M, et al. Sox2 cooperates with Chd7 to regulate genes that are mutated in human syndromes. Nat Genet. 2011;43:607–11.

    Article  CAS  PubMed  Google Scholar 

  38. Roman M, Baraibar I, Lopez I, Nadal E, Rolfo C, Vicent S, et al. KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target. Mol Cancer. 2018;17:33.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Waters AM, Der CJ. KRAS: the critical driver and therapeutic target for pancreatic cancer. Cold Spring Harb Perspect Med. 2018;8:a031435.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Schnetz MP, Bartels CF, Shastri K, Balasubramanian D, Zentner GE, Balaji R, et al. Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns. Genome Res. 2009;19:590–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Sun L, Yu R, Dang W. Chromatin architectural changes during cellular senescence and aging. Genes. 2018;9:211.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Yokoyama Y, Zhu H, Zhang R, Noma K. A novel role for the condensin II complex in cellular senescence. Cell Cycle 2015;14:2160–70.

  43. Ulianov SV, Khrameeva EE, Gavrilov AA, Flyamer IM, Kos P, Mikhaleva EA, et al. Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains. Genome Res. 2016;26:70–84.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Yokoyama Y, Zhu H, Zhang R, Noma K. A novel role for the condensin II complex in cellular senescence. Cell Cycle. 2015;14:2160–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Li W, Hu Y, Oh S, Ma Q, Merkurjev D, Song X, et al. Condensin I and II complexes license full estrogen receptor alpha-dependent enhancer activation. Mol Cell. 2015;59:188–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kagey MH, Newman JJ, Bilodeau S, Zhan Y, Orlando DA, van Berkum NL, et al. Mediator and cohesin connect gene expression and chromatin architecture. Nature. 2010;467:430–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kwong J, Chen M, Lv D, Luo N, Su W, Xiang R, et al. Induction of p38delta expression plays an essential role in oncogenic ras-induced senescence. Mol Cell Biol. 2013;33:3780–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Kanojia D, Panek WK, Cordero A, Fares J, Xiao A, Savchuk S, et al. BET inhibition increases betaIII-tubulin expression and sensitizes metastatic breast cancer in the brain to vinorelbine. Sci Transl Med. 2020;12:eaax2879.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Gyorffy B, Lanczky A, Eklund AC, Denkert C, Budczies J, Li Q, et al. An online survival analysis tool to rapidly assess the effect of 22,277 genes on breast cancer prognosis using microarray data of 1,809 patients. Breast Cancer Res Treat. 2010;123:725–31.

    Article  PubMed  Google Scholar 

  50. Romagosa C, Simonetti S, Lopez-Vicente L, Mazo A, Lleonart ME, Castellvi J, et al. p16(Ink4a) overexpression in cancer: a tumor suppressor gene associated with senescence and high-grade tumors. Oncogene. 2011;30:2087–97.

    Article  CAS  PubMed  Google Scholar 

  51. Schwartz B, Avivi-Green C, Polak-Charcon S. Sodium butyrate induces retinoblastoma protein dephosphorylation, p16 expression and growth arrest of colon cancer cells. Mol Cell Biochem. 1998;188:21–30.

    Article  CAS  PubMed  Google Scholar 

  52. Herschkowitz JI, He X, Fan C, Perou CM. The functional loss of the retinoblastoma tumour suppressor is a common event in basal-like and luminal B breast carcinomas. Breast Cancer Res. 2008;10:R75.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Dublin EA, Patel NK, Gillett CE, Smith P, Peters G, Barnes DM. Retinoblastoma and p16 proteins in mammary carcinoma: their relationship to cyclin D1 and histopathological parameters. Int J Cancer. 1998;79:71–75.

    Article  CAS  PubMed  Google Scholar 

  54. Gorgoulis VG, Zacharatos P, Kotsinas A, Liloglou T, Kyroudi A, Veslemes M, et al. Alterations of the p16-pRb pathway and the chromosome locus 9p21-22 in non-small-cell lung carcinomas: relationship with p53 and MDM2 protein expression. Am J Pathol. 1998;153:1749–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Bastide K, Guilly MN, Bernaudin JF, Joubert C, Lectard B, Levalois C, et al. Molecular analysis of the Ink4a/Rb1-Arf/Tp53 pathways in radon-induced rat lung tumors. Lung Cancer. 2009;63:348–53.

    Article  PubMed  Google Scholar 

  56. Peng J, Sun BF, Chen CY, Zhou JY, Chen YS, Chen H, et al. Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma. Cell Res. 2019;29:725–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Chen Y, Zhang Z, Yang K, Du J, Xu Y, Liu S. Myeloid zinc-finger 1 (MZF-1) suppresses prostate tumor growth through enforcing ferroportin-conducted iron egress. Oncogene. 2015;34:3839–47.

    Article  CAS  PubMed  Google Scholar 

  58. Tvingsholm SA, Hansen MB, Clemmensen KKB, Brix DM, Rafn B, Frankel LB, et al. Let-7 microRNA controls invasion-promoting lysosomal changes via the oncogenic transcription factor myeloid zinc finger-1. Oncogenesis. 2018;7:14.

    Article  PubMed  PubMed Central  Google Scholar 

  59. LaPak KM, Burd CE. The molecular balancing act of p16(INK4a) in cancer and aging. Mol Cancer Res. 2014;12:167–83.

    Article  CAS  PubMed  Google Scholar 

  60. Coppe JP, Rodier F, Patil CK, Freund A, Desprez PY, Campisi J. Tumor suppressor and aging biomarker p16(INK4a) induces cellular senescence without the associated inflammatory secretory phenotype. J Biol Chem. 2011;286:36396–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell. 1997;88:593–602.

    Article  CAS  PubMed  Google Scholar 

  62. Kotake Y, Naemura M, Murasaki C, Inoue Y, Okamoto H. Transcriptional regulation of the p16 tumor suppressor gene. Anticancer Res. 2015;35:4397–401.

    CAS  PubMed  Google Scholar 

  63. Brookes S, Rowe J, Ruas M, Llanos S, Clark PA, Lomax M, et al. INK4a-deficient human diploid fibroblasts are resistant to RAS-induced senescence. EMBO J. 2002;21:2936–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B, et al. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature. 2005;436:660–5.

    Article  CAS  PubMed  Google Scholar 

  65. Zhang Y, Tong T. FOXA1 antagonizes EZH2-mediated CDKN2A repression in carcinogenesis. Biochem Biophys Res Commun. 2014;453:172–8.

    Article  CAS  PubMed  Google Scholar 

  66. Ouyang XS, Wang X, Ling MT, Wong HL, Tsao SW, Wong YC. Id-1 stimulates serum independent prostate cancer cell proliferation through inactivation of p16(INK4a)/pRB pathway. Carcinogenesis. 2002;23:721–5.

    Article  CAS  PubMed  Google Scholar 

  67. Vishwamitra D, Curry CV, Alkan S, Song YH, Gallick GE, Kaseb AO, et al. The transcription factors Ik-1 and MZF1 downregulate IGF-IR expression in NPM-ALK(+) T-cell lymphoma. Mol Cancer. 2015;14:53.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Zhang S, Shi W, Ramsay ES, Bliskovsky V, Eiden AM, Connors D, et al. The transcription factor MZF1 differentially regulates murine Mtor promoter variants linked to tumor susceptibility. J Biol Chem. 2019;294:16756–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Li J, Liao T, Liu H, Yuan H, Ouyang T, Wang J, et al. Hypoxic glioma stem cell-derived exosomes containing linc01060 promote progression of glioma by regulating the MZF1/c-Myc/HIF1alpha axis. Cancer Res. 2021;81:114–28.

    Article  CAS  PubMed  Google Scholar 

  70. Brix DM, Tvingsholm SA, Hansen MB, Clemmensen KB, Ohman T, Siino V, et al. Release of transcriptional repression via ErbB2-induced, SUMO-directed phosphorylation of myeloid zinc finger-1 serine 27 activates lysosome redistribution and invasion. Oncogene. 2019;38:3170–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Scaglioni PP, Rabellino A, Yung TM, Bernardi R, Choi S, Konstantinidou G, et al. Translation-dependent mechanisms lead to PML upregulation and mediate oncogenic K-RAS-induced cellular senescence. EMBO Mol Med. 2012;4:594–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Campisi J, d’Adda di, Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007;8:729–40.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank the Cell Engineering and Cellular Imaging Shared Resources of WFBCCC. This study was supported by NIH/NCI grants CA131231, CA172115 and P30CA012197 (PS). PS is supported by the Anderson Oncology Research Professorship.

Author information

Author notes

  1. These authors contributed equally: Dan Wu, Hua Tan.

Authors and Affiliations

  1. Department of Cancer Biology, Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Medical Center Blvd, Winston-, Salem, NC, 27157, USA

    Dan Wu, Dongmei Cheng, Guanwen Wang, Juan Wang, Ding A. Ma, George M. Dong & Peiqing Sun

  2. School of Biomedical Informatics, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA

    Hua Tan

  3. Nankai University School of Medicine, Tianjin, China

    Weijun Su, Guanwen Wang & Juan Wang

Authors
  1. Dan Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hua Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Weijun Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dongmei Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Guanwen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Juan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ding A. Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. George M. Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Peiqing Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DW, HT, WS and PS conceived and designed the study. DW, HT, WS, DC, GW, JW, DAM and GMD executed the experiments; DW, HT, WS, DAM, GMW and PS analyzed and interpreted the data. DW, HT and PS wrote and/or reviewed the manuscript.

Corresponding author

Correspondence to Peiqing Sun.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, D., Tan, H., Su, W. et al. MZF1 mediates oncogene-induced senescence by promoting the transcription of p16INK4A. Oncogene 41, 414–426 (2022). https://doi.org/10.1038/s41388-021-02110-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41388-021-02110-y

This article is cited by

Search

Advanced search

Quick links