TITLE

LIFR functions as a metastasis suppressor in hepatocellular carcinoma by negatively regulating phosphoinositide 3-kinase/AKT pathway

AUTHOR(S)
Qin Luo; Cun Wang; Guangzhi Jin; Dishui Gu; Ning Wang; Jin Song; Haojie Jin; Fangyuan Hu; Yurong Zhang; Tianxiang Ge; Xisong Huo; Wei Chu; Huiqun Shu; Jingyuan Fang; Ming Yao; Jianren Gu; Wenming Cong; Wenxin Qin
PUB. DATE
October 2015
SOURCE
Carcinogenesis;Oct2015, Vol. 36 Issue 10, p1201
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Hepatocellular carcinoma (HCC) is one of the leading causes for cancer related mortality worldwide. Poor prognosis of HCC patients is mainly due to frequent metastasis and recurrence. Deregulation of metastasis suppressors in malignant cells plays critical roles during cancer metastasis. Thus, novel metastasis suppressors are urgently needed to be uncovered to shed new light on molecular mechanisms driving HCC metastasis. In the present study, decreased expression of leukemia inhibitory factor receptor (LIFR) was demonstrated in HCC, and its expression levels were even lower in HCC with metastasis. Downregulated LIFR expression predicted poor prognosis in HCC patients. LIFR was an independent and significant risk factor for their recurrence and survival. Silencing LIFR resulted in forced metastasis of HCC cells, whereas ectopic overexpression of LIFR attenuated migration and invasion of HCC cells in vitro and in vivo. Moreover, LIFR knockdown could activate phosphoinositide 3-kinase/V-akt Murine Thymoma Viral Oncogene Homolog (PI3K/AKT) signaling through enhancing phosphorylation of Janus kinase 1 (JAK1), which successively promoted matrix metalloproteinase 13 (MMP13) expression and HCC metastasis. Combination of LIFR and p-AKT or MMP13 was a more powerful predictor of poor prognosis for HCC patients. Together, these findings conclude that LIFR functions as a novel metastasis suppressor in HCC and may serve as a prognostic biomarker for HCC patients.
ACCESSION #
110199533

 

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