Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA279355 | ENA |
REPOSITORIES: ENA
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Project description:Prostate cancer is a common cause of cancer-related death in men. E6AP, an E3 ubiquitin ligase and a transcription cofactor, is elevated in a subset of prostate cancer patients. Genetic manipulations of E6AP in prostate cancer cells expose a role of E6AP in promoting growth and survival of prostate cancer cells in vitro and in vivo. However, the effect of E6AP on prostate cancer cells is broad and it cannot be explained fully by previously identified tumour suppressors, promyelocytic leukemia protein and p27, that are regulated by E6AP. To explore additional players that are regulated downstream of E6AP, we combined a transcriptomic and proteomic approaches. We identified and quantified 16,130 transcripts and 7,209 proteins in castration resistant prostate cancer cell line, DU145. A total of 2,763 transcripts and 308 proteins were considered significantly altered upon knockdown of E6AP. Pathway analyses supported the known phenotypic effect of E6AP knockdown in prostate cancer cells and in parallel exposed novel potential links of E6AP with cancer metabolism, DNA damage repair and immune response. Changes in expression of the top candidates were confirmed using real-time polymerase chain reaction. Of these, clusterin, a stress-induced chaperone protein commonly deregulated in prostate cancer was pursued further. Knockdown of E6AP resulted in increased clusterin transcript and protein levels in vitro and in vivo. Concomitant knockdown of E6AP and clusterin supported the contribution of clusterin to the phenotype induced by E6AP. Overall, results from this study provide insight intothe potential biological pathways controlled by E6AP in prostate cancer cells and identifies clusterin as a novel target of E6AP.
2018-02-27 | PXD008743 | Pride
Project description:Prostate cancer is a common cause of cancer-related death in men. E6AP, an E3 ubiquitin ligase and a transcription cofactor, is elevated in a subset of prostate cancer patients. Genetic manipulations of E6AP in prostate cancer cells expose a role of E6AP in promoting growth and survival of prostate cancer cells in vitro and in vivo. However, the effect of E6AP on prostate cancer cells is broad and it cannot be explained fully by previously identified tumour suppressors, promyelocytic leukemia protein and p27, that are regulated by E6AP. To explore additional players that are regulated downstream of E6AP, we combined a transcriptomic and proteomic approaches. We identified and quantified 16,130 transcripts and 7,209 proteins in castration resistant prostate cancer cell line, DU145. A total of 2,763 transcripts and 308 proteins were considered significantly altered upon knockdown of E6AP. Pathway analyses supported the known phenotypic effect of E6AP knockdown in prostate cancer cells and in parallel exposed novel potential links of E6AP with cancer metabolism, DNA damage repair and immune response. Changes in expression of the top candidates were confirmed using real-time polymerase chain reaction. Of these, clusterin, a stress-induced chaperone protein commonly deregulated in prostate cancer was pursued further. Knockdown of E6AP resulted in increased clusterin transcript and protein levels in vitro and in vivo. Concomitant knockdown of E6AP and clusterin supported the contribution of clusterin to the phenotype induced by E6AP. Overall, results from this study provide insight intothe potential biological pathways controlled by E6AP in prostate cancer cells and identifies clusterin as a novel target of E6AP.
2021-03-11 | PXD008132 | Pride
Project description:Prostate cancer is a common cause of cancer-related death in men. E6AP, an E3 ubiquitin ligase and a transcription cofactor, is elevated in a subset of prostate cancer patients. Genetic manipulations of E6AP in prostate cancer cells expose a role of E6AP in promoting growth and survival of prostate cancer cells in vitro and in vivo. However, the effect of E6AP on prostate cancer cells is broad and it cannot be explained fully by previously identified tumour suppressor targets of E6AP, promyelocytic leukemia protein and p27. To explore additional players that are regulated downstream of E6AP, we combined a transcriptomic and proteomic approaches. We identified and quantified 16,130 transcripts and 7,209 proteins in castration resistant prostate cancer cell line, DU145. A total of 2,763 transcripts and 308 proteins were significantly altered upon knockdown of E6AP. Pathway analyses supported the known phenotypic effects of E6AP knockdown in prostate cancer cells and in parallel exposed novel potential links of E6AP with cancer metabolism, DNA damage repair and immune response. Changes in expression of the top candidates were confirmed using real-time polymerase chain reaction. Of these, clusterin, a stress-induced chaperone protein, commonly deregulated in prostate cancer, was pursued further. Knockdown of E6AP resulted in increased clusterin transcript and protein levels in vitro and in vivo. Concomitant knockdown of E6AP and clusterin supported the contribution of clusterin to the phenotype induced by E6AP. Overall, results from this study provide insight into the potential biological pathways controlled by E6AP in prostate cancer cells and identifies clusterin as a novel target of E6AP.
2017-11-27 | GSE107245 | GEO
Project description:Clusterin (CLU) is a stress-activated molecular chaperone that confers treatment resistance to taxanes when highly expressed. While CLU inhibition potentiates activity of taxanes and other anti-cancer therapies in preclinical models, progression to treatment resistant disease still occurs implicating additional compensatory survival mechanisms. Taxanes are believed to selectively target cells in mitosis, a complex mechanism controlled in part by balancing antagonistic roles of Cdc25C and Wee1 in mitosis progression. Our data indicate that CLU silencing induces a constitutive activation of Cdc25C, which delays mitotic exit and hence sensitizes cancer cells to mitotic-targeting agents such taxanes. Unchecked Cdc25C activation leads to mitotic catastrophe and cell death unless cells upregulate protective mechanisms mediated through the cell cycle regulators Wee1 and Cdc2. In this study we show that CLU silencing induces a constitutive activation of Cdc25C via the phosphatase PP2A but leads to relief of negative feedback inhibition and activation of Wee1-Cdc2 to promote survival and limit therapeutic efficacy. Simultaneous inhibition of CLU-regulated cell cycle effectors, like PP2A and Wee1, may improve synergistic responses of biologically rational combinatorial regimens using taxanes and CLU inhibitors Biological triplicate of PC3 treated with siClusterin were compared to biological trplicate of PC3 treated with siScramblein
2016-03-01 | E-GEOD-67256 | biostudies-arrayexpress
Project description:Lipid catabolism inhibition sensitizes prostate cancer cells to antiandrogen blockade
| PRJNA326312 | ENA
Project description:Comparison of the new generation taxane cabazitaxel with docetaxel in prostate cancer cells Cabazitaxel impacts distint molecular pathways as compared to docetaxel, which could underlie its efficacy after docetaxel treatment has failed in castration resistant prostate cancer patients
2015-01-01 | GSE63478 | GEO
Project description:Comparison of the new generation taxane cabazitaxel with docetaxel in prostate cancer cells Cabazitaxel impacts distint molecular pathways as compared to docetaxel, which could underlie its efficacy after docetaxel treatment has failed in castration resistant prostate cancer patients
2015-01-01 | GSE63477 | GEO