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Browse SPP1

Summary
SymbolSPP1
Namesecreted phosphoprotein 1
Aliases BSPI; ETA-1; early T-lymphocyte activation 1; OPN; osteopontin; bone sialoprotein I; SPP1/CALPHA1 fusion; ne ......
Chromosomal Location4q22.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Secreted.
Domain PF00865 Osteopontin
Function

Binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction.; FUNCTION: Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin-12 and reducing production of interleukin-10 and is essential in the pathway that leads to type I immunity.

> Gene Ontology
 
Biological Process GO:0001503 ossification
GO:0001558 regulation of cell growth
GO:0001649 osteoblast differentiation
GO:0001890 placenta development
GO:0001893 maternal placenta development
GO:0001894 tissue homeostasis
GO:0007409 axonogenesis
GO:0007565 female pregnancy
GO:0007566 embryo implantation
GO:0007584 response to nutrient
GO:0008361 regulation of cell size
GO:0009991 response to extracellular stimulus
GO:0010721 negative regulation of cell development
GO:0010769 regulation of cell morphogenesis involved in differentiation
GO:0010771 negative regulation of cell morphogenesis involved in differentiation
GO:0010975 regulation of neuron projection development
GO:0010977 negative regulation of neuron projection development
GO:0016049 cell growth
GO:0022604 regulation of cell morphogenesis
GO:0022617 extracellular matrix disassembly
GO:0030198 extracellular matrix organization
GO:0030308 negative regulation of cell growth
GO:0031099 regeneration
GO:0031102 neuron projection regeneration
GO:0031103 axon regeneration
GO:0031214 biomineral tissue development
GO:0031345 negative regulation of cell projection organization
GO:0031667 response to nutrient levels
GO:0032102 negative regulation of response to external stimulus
GO:0032535 regulation of cellular component size
GO:0032844 regulation of homeostatic process
GO:0032846 positive regulation of homeostatic process
GO:0033273 response to vitamin
GO:0033280 response to vitamin D
GO:0034103 regulation of tissue remodeling
GO:0034105 positive regulation of tissue remodeling
GO:0043062 extracellular structure organization
GO:0044706 multi-multicellular organism process
GO:0045124 regulation of bone resorption
GO:0045453 bone resorption
GO:0045665 negative regulation of neuron differentiation
GO:0045780 positive regulation of bone resorption
GO:0045926 negative regulation of growth
GO:0046697 decidualization
GO:0046849 bone remodeling
GO:0046850 regulation of bone remodeling
GO:0046852 positive regulation of bone remodeling
GO:0048545 response to steroid hormone
GO:0048588 developmental cell growth
GO:0048608 reproductive structure development
GO:0048638 regulation of developmental growth
GO:0048640 negative regulation of developmental growth
GO:0048667 cell morphogenesis involved in neuron differentiation
GO:0048668 collateral sprouting
GO:0048670 regulation of collateral sprouting
GO:0048671 negative regulation of collateral sprouting
GO:0048673 collateral sprouting of intact axon in response to injury
GO:0048678 response to axon injury
GO:0048679 regulation of axon regeneration
GO:0048681 negative regulation of axon regeneration
GO:0048683 regulation of collateral sprouting of intact axon in response to injury
GO:0048685 negative regulation of collateral sprouting of intact axon in response to injury
GO:0048771 tissue remodeling
GO:0048871 multicellular organismal homeostasis
GO:0050768 negative regulation of neurogenesis
GO:0050770 regulation of axonogenesis
GO:0050771 negative regulation of axonogenesis
GO:0051961 negative regulation of nervous system development
GO:0060135 maternal process involved in female pregnancy
GO:0060249 anatomical structure homeostasis
GO:0060560 developmental growth involved in morphogenesis
GO:0061387 regulation of extent of cell growth
GO:0061458 reproductive system development
GO:0061564 axon development
GO:0070570 regulation of neuron projection regeneration
GO:0070571 negative regulation of neuron projection regeneration
GO:0090066 regulation of anatomical structure size
GO:1903034 regulation of response to wounding
GO:1903035 negative regulation of response to wounding
Molecular Function GO:0005125 cytokine activity
GO:0050840 extracellular matrix binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04151 PI3K-Akt signaling pathway
hsa04510 Focal adhesion
hsa04512 ECM-receptor interaction
hsa04620 Toll-like receptor signaling pathway
Reactome R-HSA-1474228: Degradation of the extracellular matrix
R-HSA-1474244: Extracellular matrix organization
R-HSA-216083: Integrin cell surface interactions
R-HSA-162582: Signal Transduction
R-HSA-186797: Signaling by PDGF
Summary
SymbolSPP1
Namesecreted phosphoprotein 1
Aliases BSPI; ETA-1; early T-lymphocyte activation 1; OPN; osteopontin; bone sialoprotein I; SPP1/CALPHA1 fusion; ne ......
Chromosomal Location4q22.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between SPP1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between SPP1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
25273090Colon CarcinomaInhibit immunity (T cell function)Tumor-derived osteopontin suppresses antitumor immunity by promoting extramedullary myelopoiesis. In this study, we found that osteopontin expressed by tumor cells enhances extramedullary myelopoiesis in a CD44-dependent manner through the Erk1/2-MAPK pathway.
25035397Lung carcinomasInhibit immunity (T cell function)The matricellular protein osteopontin (OPN, Spp-1) is widely associated with cancer aggressiveness when produced by tumor cells, but its impact is uncertain when produced by leukocytes in the context of the tumor stroma.Moreover, fewer regulatory T cells accumulated at the metastatic site in Spp1(-/-) mice.
24935458leukemiaPromote immunity (infiltration)A high level of OPN in EL4-v10 tumors supported leukocyte recruitment and tumor-infiltrating T-cell activation.
27601131Prostate AdenocarcinomaPromote immunityOsteopontin has a protective role in prostate tumor development in mice. Osteopontin (OPN) is a protein, generally considered to play a pro-tumorigenic role, whereas several reports have demonstrated the anti-tumorigenic function of OPN during tumor development. Here, we report that host-derived OPN plays an anti-tumorigenic role in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model and a TRAMP tumor transplant model. Tumor suppression mediated by OPN in Rag2-/- mice suggests that OPN is dispensable in the adaptive immune response.
29745428Ovarian CarcinomaPromote immunitySKOV3 and OVCAR8, human ovarian carcinoma cell lines, exhibited enhanced proliferation in conditioned media from HE4-exposed PBMCs, an effect that was attenuated by the addition of recombinant OPN or OPN-inducible cytokines (IL-12 and IFN-γ). In these biopsy specimens, the number of OPN+ T cells correlated positively with progression free survival (PFS) and inversely with serum HE4 level.
Summary
SymbolSPP1
Namesecreted phosphoprotein 1
Aliases BSPI; ETA-1; early T-lymphocyte activation 1; OPN; osteopontin; bone sialoprotein I; SPP1/CALPHA1 fusion; ne ......
Chromosomal Location4q22.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of SPP1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolSPP1
Namesecreted phosphoprotein 1
Aliases BSPI; ETA-1; early T-lymphocyte activation 1; OPN; osteopontin; bone sialoprotein I; SPP1/CALPHA1 fusion; ne ......
Chromosomal Location4q22.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of SPP1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0550.951
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.6590.872
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.4030.885
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.6090.488
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.7790.712
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.3780.9
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.8240.336
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-1.8440.506
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.4320.881
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-1.2240.748
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 28-2.3350.688
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.1350.648
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of SPP1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277301.4-1.41
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275901.7-1.71
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.509.50.492
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.707.71
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38277.907.90.26
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 221313.6013.60.279
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11139.109.10.458
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 6116.7016.71
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolSPP1
Namesecreted phosphoprotein 1
Aliases BSPI; ETA-1; early T-lymphocyte activation 1; OPN; osteopontin; bone sialoprotein I; SPP1/CALPHA1 fusion; ne ......
Chromosomal Location4q22.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of SPP1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolSPP1
Namesecreted phosphoprotein 1
Aliases BSPI; ETA-1; early T-lymphocyte activation 1; OPN; osteopontin; bone sialoprotein I; SPP1/CALPHA1 fusion; ne ......
Chromosomal Location4q22.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of SPP1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by SPP1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolSPP1
Namesecreted phosphoprotein 1
Aliases BSPI; ETA-1; early T-lymphocyte activation 1; OPN; osteopontin; bone sialoprotein I; SPP1/CALPHA1 fusion; ne ......
Chromosomal Location4q22.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of SPP1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolSPP1
Namesecreted phosphoprotein 1
Aliases BSPI; ETA-1; early T-lymphocyte activation 1; OPN; osteopontin; bone sialoprotein I; SPP1/CALPHA1 fusion; ne ......
Chromosomal Location4q22.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of SPP1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolSPP1
Namesecreted phosphoprotein 1
Aliases BSPI; ETA-1; early T-lymphocyte activation 1; OPN; osteopontin; bone sialoprotein I; SPP1/CALPHA1 fusion; ne ......
Chromosomal Location4q22.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between SPP1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolSPP1
Namesecreted phosphoprotein 1
Aliases BSPI; ETA-1; early T-lymphocyte activation 1; OPN; osteopontin; bone sialoprotein I; SPP1/CALPHA1 fusion; ne ......
Chromosomal Location4q22.1
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting SPP1 collected from DrugBank database.
> Drugs from DrugBank database
 

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