C-Myc targeted genes validated by PCR array in STEAP1-silenced HepG2 cells.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE173813 | GEO | 2021/05/05
REPOSITORIES: GEO
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Project description:c-Myc targeted genes validated by PCR array in STEAP1-silenced HepG2 cells.
| PRJNA727168 | ENA
Project description:Goal: identification of differentially expressed genes after STEAP1 silencing. Ewing tumors (ET) are characterized by oncogenic EWS/ETS translocations and early metastasis. STEAP1 is a membrane-bound channel protein of unkown function. While overexpressed in many cancers, STEAP1 expression is strongly restricted to mesenchymal stem cells, prostate and urothelium among benign tissues. Here we show that STEAP1 is a direct transcriptional target of EWS/FLI1 and critical for ET malignancy. We demonstrate that STEAP1 is most prominently expressed in ET among sarcomas and provide further evidence for the concept of STEAP1 as a universal diagnostic marker for carcinomas. Using RNA interference we determined that STEAP1 promotes cellular invasiveness and anchorage-independent growth in vitro and accelerates tumor growth and metastasis in vivo. Transcriptome and proteome analyses as well as functional studies reveal that STEAP1 contributes to the generation of reactive oxygen species that in turn regulate the levels of redox-sensitive signaling molecules and pro-metatstatic genes. In synopsis, these data illuminate the hitherto unkown oncogenic function of STEAP1 as a redox-modulator in ET and point to a potential role of STEAP1 as universal drug target for anti-cancer therapy. 6 samples (3x A673 cells; 3x SK-N-MC cells); for each cell line one sample was transfected with control non silencing siRNA and two samples with different STEAP1 siRNAs (siSTEAP1_2 and siSTEAP1_3).
2012-01-01 | E-GEOD-26422 | biostudies-arrayexpress
Project description:Goal: identification of differentially expressed genes after STEAP1 silencing. Ewing tumors (ET) are characterized by oncogenic EWS/ETS translocations and early metastasis. STEAP1 is a membrane-bound channel protein of unkown function. While overexpressed in many cancers, STEAP1 expression is strongly restricted to mesenchymal stem cells, prostate and urothelium among benign tissues. Here we show that STEAP1 is a direct transcriptional target of EWS/FLI1 and critical for ET malignancy. We demonstrate that STEAP1 is most prominently expressed in ET among sarcomas and provide further evidence for the concept of STEAP1 as a universal diagnostic marker for carcinomas. Using RNA interference we determined that STEAP1 promotes cellular invasiveness and anchorage-independent growth in vitro and accelerates tumor growth and metastasis in vivo. Transcriptome and proteome analyses as well as functional studies reveal that STEAP1 contributes to the generation of reactive oxygen species that in turn regulate the levels of redox-sensitive signaling molecules and pro-metatstatic genes. In synopsis, these data illuminate the hitherto unkown oncogenic function of STEAP1 as a redox-modulator in ET and point to a potential role of STEAP1 as universal drug target for anti-cancer therapy.
2012-01-01 | GSE26422 | GEO
Project description:Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is a compelling tumor-associated cell surface antigen for therapeutic targeting in solid tumors. Here, we identified broad expression of STEAP1 relative to the established theranostic target prostate-specific membrane antigen (PSMA) in a series of lethal metastatic prostate cancers which prompted the development of a STEAP1-directed chimeric antigen receptor (CAR) T cell therapy. STEAP1 CAR T cells demonstrated reactivity in low antigen density, antitumor activity across multiple metastatic human and mouse prostate cancer models, and preliminary safety in a human STEAP1 knock-in mouse model. In human-in-mouse and mouse-in-mouse studies, STEAP1 CAR T cell therapy yielded effective tumor responses, but antigen escape was appreciated as a recurrent mechanism of treatment resistance and STEAP1 antigen loss was associated with diminished tumor antigen processing and presentation. The application of tumor-localized interleukin-12 (IL-12) therapy in the form of a collagen binding domain (CBD)-IL-12 fusion protein as an adjunct to STEAP1 CAR T cell therapy enhanced antitumor efficacy by remodeling the immunologically cold tumor microenvironment of prostate cancer and combating STEAP1 antigen escape through the engagement of host immunity and epitope spreading. In summary, we describe the extent of STEAP1 expression in treatment-refractory metastatic prostate cancer, characterize a STEAP1 CAR T cell therapy with preclinical evidence of potency and safety, and nominate a combinatorial immunotherapy strategy to overcome barriers to the efficacy of CAR T cell therapy in advanced prostate cancer.
2023-03-22 | GSE214584 | GEO
Project description:Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is a compelling tumor-associated cell surface antigen for therapeutic targeting in solid tumors. Here, we identified broad expression of STEAP1 relative to the established theranostic target prostate-specific membrane antigen (PSMA) in a series of lethal metastatic prostate cancers which prompted the development of a STEAP1-directed chimeric antigen receptor (CAR) T cell therapy. STEAP1 CAR T cells demonstrated reactivity in low antigen density, antitumor activity across multiple metastatic human and mouse prostate cancer models, and preliminary safety in a human STEAP1 knock-in mouse model. In human-in-mouse and mouse-in-mouse studies, STEAP1 CAR T cell therapy yielded effective tumor responses, but antigen escape was appreciated as a recurrent mechanism of treatment resistance and STEAP1 antigen loss was associated with diminished tumor antigen processing and presentation. The application of tumor-localized interleukin-12 (IL-12) therapy in the form of a collagen binding domain (CBD)-IL-12 fusion protein as an adjunct to STEAP1 CAR T cell therapy enhanced antitumor efficacy by remodeling the immunologically cold tumor microenvironment of prostate cancer and combating STEAP1 antigen escape through the engagement of host immunity and epitope spreading. In summary, we describe the extent of STEAP1 expression in treatment-refractory metastatic prostate cancer, characterize a STEAP1 CAR T cell therapy with preclinical evidence of potency and safety, and nominate a combinatorial immunotherapy strategy to overcome barriers to the efficacy of CAR T cell therapy in advanced prostate cancer.
2023-04-03 | GSE228884 | GEO
Project description:Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is a compelling tumor-associated cell surface antigen for therapeutic targeting in solid tumors. Here, we identified broad expression of STEAP1 relative to the established theranostic target prostate-specific membrane antigen (PSMA) in a series of lethal metastatic prostate cancers which prompted the development of a STEAP1-directed chimeric antigen receptor (CAR) T cell therapy. STEAP1 CAR T cells demonstrated reactivity in low antigen density, antitumor activity across multiple metastatic human and mouse prostate cancer models, and preliminary safety in a human STEAP1 knock-in mouse model. In human-in-mouse and mouse-in-mouse studies, STEAP1 CAR T cell therapy yielded effective tumor responses, but antigen escape was appreciated as a recurrent mechanism of treatment resistance and STEAP1 antigen loss was associated with diminished tumor antigen processing and presentation. The application of tumor-localized interleukin-12 (IL-12) therapy in the form of a collagen binding domain (CBD)-IL-12 fusion protein as an adjunct to STEAP1 CAR T cell therapy enhanced antitumor efficacy by remodeling the immunologically cold tumor microenvironment of prostate cancer and combating STEAP1 antigen escape through the engagement of host immunity and epitope spreading. In summary, we describe the extent of STEAP1 expression in treatment-refractory metastatic prostate cancer, characterize a STEAP1 CAR T cell therapy with preclinical evidence of potency and safety, and nominate a combinatorial immunotherapy strategy to overcome barriers to the efficacy of CAR T cell therapy in advanced prostate cancer.
2023-03-22 | GSE214583 | GEO
Project description:Prostate cancer (PCa) continues to be one of the most common cancers in men worldwide. The six transmembrane epithelial antigen of the prostate 1 (STEAP1) protein is overexpressed in several types of human tumours, particularly in PCa. Our research group has demonstrated that STEAP1 overexpression is associated with PCa progression and aggressiveness. Therefore, understanding the cellular and molecular mechanisms triggered by STEAP1 overexpression will provide important insights to delineate new strategies for PCa treatment. In the present work, a proteomic strategy was used to characterize the intracellular signalling pathways and the molecular targets downstream of STEAP1 in PCa cells. A label-free approach was applied using an Orbitrap LC-MS/MS system to characterize the proteome of STEAP1-knockdown PCa cells. More than 6700 proteins were identified, of which a total of 526 proteins were found differentially expressed in scramble siRNA versus STEAP1 siRNA (234 proteins up-regulated and 292 proteins down-regulated). Bioinformatics analysis allowed us to explore the mechanism through which STEAP1 exerts influence on PCa, revelling that endocytosis, RNA transport, apoptosis, aminoacyl-tRNA biosynthesis and metabolic pathways are the biological processes where STEAP1 is involved. By immunoblotting, it was confirmed that STEAP1 knockdown induced the up-regulation of cathepsin B, intersectin-1 and syntaxin 4,while it down-regulation HRas, PIK3C2A and DIS3. These finding suggested that blocking STEAP1 might be a strategy to activate apoptosis and endocytosis, and diminish cellular metabolism and intercellular communication, leading to inhibition of PCa progression.
2023-10-18 | PXD037834 | Pride
Project description:RNA-seq was performed to confirm the effect of dMyc overexpression or RNAi repression on conserved Myc targets in the Drosophila wing disc.
2022-04-26 | E-MTAB-9328 | biostudies-arrayexpress
Project description:To identify proteomic signatures associated with hepatocellular carcinoma driven by MYC overexpression, proteomics was performed on the LAP-tTA/tetO-MYC mouse conditional liver cancer model. Upon MYC activation, mice form liver cancer. Differential proteomics was performed in "MYC on" (MYC-HCC) mouse liver tumors versus mouse control normal liver tissue (where MYC was not overexpressed to drive tumorigenesis -- "MYC off").
2022-10-12 | PXD031478 | Pride
Project description:Mechanisitc model of PI3K and ERK signal integration by Myc. ERK and PI3K regulated Myc satbility by phosphorylating the same. (PMID:18463697)
2024-09-02 | BIOMD0000000818 | BioModels