• Biologie

  • Progression et métastases

  • Colon-rectum

Overexpression of Sirt7 exhibits oncogenic property and serves as a prognostic factor in colorectal cancer

Menée in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels la sirtuine Sirt7 favorise le développement et la progression d'un cancer colorectal

Purpose: Sirtuins play an important role in cancer development. Sirt7, as a member of this family, is frequently overexpressed in certain carcinomas, but the oncogenic mechanism is seldom reported. In this study, Sirt7 was characterized for its role in colorectal cancer (CRC) aggressiveness and underlying molecular mechanisms. Experimental Design: Quantitative PCR, Western blotting and immunohistochemistry were performed to study Sirt7 expression in a cohort of CRC tissues and non-tumor tissues and cells. A series of in-vitro and in-vivo assays was performed to elucidate the function of Sirt7 in CRC and its underlying mechanisms. Association between the Sirt7 signature and survival were examined using Kaplan-Meier analysis and log-rank tests. Results: The Sirt7 protein level significantly correlated with tumor stage (p=0.029), lymph node metastasis (p=0.046) and poor patient survival (p<0.05). Sirt7 knockdown significantly inhibited CRC cell proliferation, colony formation and motility. Ectopic Sirt7 expression promoted colony formation, induced a more invasive phenotype and accelerated cell growth both in vitro and in vivo. Moreover, Sirt7 enhanced MAPK pathway activity concomitantly with p-ERK and p-MEK upregulation. In Sirt7-overexpressing cells, the mesenchymal markers vimentin and fibronectin were upregulated, and the epithelial markers E-cadherin and β-catenin were downregulated, which was linked to enhanced invasion by CRC cells. Conclusion: Our findings suggest that Sirt7 plays an important role in the development and progression of human CRC and functions as a valuable marker of CRC prognosis.

Clinical Cancer Research 2014

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