Open AccessSIRT1 facilitates hepatocellular carcinoma metastasis by promoting PGC-1α-mediated mitochondrial biogenesis
Author(s) -
Yuming Li,
Shangcheng Xu,
Jing Li,
Zheng Lu,
Min Feng,
Xiaoya Wang,
Ke Han,
Huifeng Pi,
Min Li,
Xiaobing Huang,
Nan You,
Y Tian,
Zuo Guo-hua,
Hongyan Li,
Hongzhi Zhao,
Ping Deng,
Zhengping Yu,
Zhou Zhou,
Ping Liang
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.8711
Subject(s) - cancer research , gene knockdown , metastasis , downregulation and upregulation , mitochondrial biogenesis , ectopic expression , mitochondrion , biology , sirtuin 1 , hepatocellular carcinoma , transplantation , medicine , cancer , cell culture , microbiology and biotechnology , gene , biochemistry , genetics
SIRT1 is a multifaceted NAD+-dependent protein deacetylase known to act as a tumor promoter or suppressor in different cancers. Here, we describe a novel mechanism of SIRT1-induced hepatocellular carcinoma (HCC) metastasis. SIRT1 overexpression was frequently detected in human HCC specimens and was associated with microvascular invasion (P = 0.0039), advanced tumor node metastasis (TNM) stages (P = 0.0016), HCC recurrence (P = 0.021) and poor outcomes (P = 0.039). Lentivirus-mediated knockdown of SIRT1 in MHCC97H cells reduced invasion and metastasis in vitro and in vivo. SIRT1 depletion attenuated mitochondrial biogenesis and adenosine triphosphate (ATP) production but did not affect epithelial-mesenchymal transition. Elevated SIRT1 expression strongly correlated with the upregulation of PGC-1α in HCC specimens, and ectopic expression of SIRT1 increased PGC-1α levels. In cell assays and an orthotopic transplantation model, PGC-1α overexpression reversed the inhibitory effects of SIRT1 depletion on invasion and metastasis by enhancing mitochondrial biogenesis. These findings reveal the involvement of SIRT1 in HCC metastasis and provide a rationale for exploring therapeutic targets against the SIRT1/PGC-1α axis.