| Literature DB >> 26975631 |
Feifei Cheng1, Li Su2, Chao Yao2, Limei Liu2, Junjie Shen2, Chungang Liu2, Xuejiao Chen2, Yongli Luo2, Lupin Jiang2, Juanjuan Shan2, Jun Chen2, Wei Zhu2, Jimin Shao3, Cheng Qian4.
Abstract
Understanding molecular mechanisms of colorectal cancer (CRC) metastasis is urgently required for targeted therapy and prognosis of metastatic CRC. In this study, we explored potential effects of silent mating type information regulation 2 homolog 1 (SIRT1) on CRC metastasis. Our data showed that ectopic expression of SIRT1 markedly increased the migration and invasion of CRC cells. In contrast, silencing SIRT1 repressed this behavior in aggressive CRC cells. Tumor xenograft experiments revealed that knockdown of SIRT1 impaired CRC metastasis in vivo. Silencing SIRT1 in CRC cells induced mesenchymal-epithelial transition (MET), which is the reverse process of epithelial-mesenchymal transition (EMT) and characterized by a gain of epithelial and loss of mesenchymal markers. We provided a mechanistic insight toward regulation of Fra-1 by SIRT1 and demonstrated a direct link between the SIRT1-Fra-1 axis and EMT. Moreover, SIRT1 expression correlated positively with Fra-1 expression, metastasis and overall survival in patients with CRC. Taken together, our data provide a novel mechanistic role of SIRT1 in CRC metastasis, suggesting that SIRT1 may serve as a potential therapeutic target for metastatic CRC.Entities:
Keywords: Colorectal cancer; Epithelial–mesenchymal transition; Fra-1; Metastasis; SIRT1
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Year: 2016 PMID： 26975631 DOI： 10.1016/j.canlet.2016.03.010
Source DB: PubMed Journal: Cancer Lett ISSN： 0304-3835 Impact factor: 8.679