Hypoxia upregulates Rab11-family interacting protein 4 through HIF-1α to promote the metastasis of hepatocellular carcinoma

Oncogene
F HuW Qin

Abstract

Hypoxic microenvironment is a powerful driving force for the invasion and metastasis of hepatocellular carcinoma (HCC). Hypoxia-inducible factor 1α (HIF-1α), as a crucial regulator of transcriptional responses to hypoxia, induces the expression of multiple target genes involved in different steps of HCC metastatic process. It is critical to find target genes associated with metastasis under hypoxia for shedding new light on molecular mechanism of HCC metastasis. In this study, we uncovered that hypoxia could induce the upregulation of Rab11-family interacting protein 4 (Rab11-FIP4) and activation of Rab11-FIP4 promoter by HIF-1α. The overexpression of Rab11-FIP4 significantly enhanced the mobility and invasiveness of HCC cells in vitro, also contributed to distant lung metastasis in vivo, whereas silencing of Rab11-FIP4 decreased the ability of migration and invasion in HCC cells in vitro and suppressed lung metastasis in vivo. Rab11-FIP4 facilitated HCC metastasis through the phosphorylation of PRAS40, which was regulated by mTOR. Furthermore, the expression level of Rab11-FIP4 was significantly increased in HCC tissues and high expression of Rab11-FIP4 was closely correlated with vascular invasion and poor prognosis in HCC pa...Continue Reading

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Citations

Jan 23, 2016·Biochemical and Biophysical Research Communications·Chang-Long XuBo Zheng
Mar 1, 2017·Molecular Pharmacology·Xin Xin XiongXiao Qian Chen
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Jul 3, 2021·International Journal of Molecular Sciences·Maria J IraburuCristina Montiel-Duarte

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