Abstract
Predictive biomarkers for advanced prostate cancer (PCa) are still missing. The sirtuin 7 (SIRT7) has been linked to tumorogenesis but its role in prostate cancer is poorly documented. To determine if SIRT7 can be a biomarker for aggressive prostate cancer and plays a role in PCa aggressiveness. We analyzed the expression of SIRT7 by immunohistochemistry in 57 patients comparing healthy with adjacent cancer tissue. SIRT7 levels were significantly elevated in tumors and its expression was positively associated with the grade. We also demonstrated that the knock down of SIRT7 decreased the migration of DU145 and PC3 cells (two androgen-independent prostate cancer cell lines) whereas the overexpression of the native protein but not the mutated form increased the cell migration and the invasion of the poorly aggressive prostate cancer cell line LNCaP. Finally, we also showed that SIRT7 overexpression induced the resistance to docetaxel. Our results demonstrate that SIRT7 promotes prostate cancer cell aggressiveness and chemoresistance and suggest that SIRT7 is a good predictive biomarker of PCa aggressiveness.
Highlights
Prostate cancer (PCa) is one of the leading cause of death by cancer in men
We demonstrated that the knock down of sirtuin 7 (SIRT7) decreased the migration of DU145 and PC3 cells whereas the overexpression of the native protein but not the mutated form increased the cell migration and the invasion of the poorly aggressive prostate cancer cell line LNCaP
We have demonstrated that SIRT7 plays an important role in the aggressiveness of prostate cancer
Summary
Prostate cancer (PCa) is one of the leading cause of death by cancer in men. Effective surgical and radiation treatments exist for localized PCa, metastatic PCa remains mostly incurable. A major issue is to predict whether localized PCa will become metastatic, markers of aggressiveness in PCa are needed. The process of metastasis is complex, it involves multiple biological processes, including angiogenesis, local migration and invasion, of tumor cells [1]. PCa cell migration and invasion are regulated by numerous proteins including the transcription factor Slug/snail, the glycoprotein fibronectin (FN) and the intermediate filament Vimentin [2]. Fibronectin has been shown to induce the expression of the matrix metalloproteinases expression 2 [3] and blocking FN with anti-FN antibodies resulted in a significant decrease in adhesion of LNCaP prostate cancer cells [4]
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