RRC ID 38110
Author Luo Q, Wang C, Jin G, Gu D, Wang N, Song J, Jin H, Hu F, Zhang Y, Ge T, Huo X, Chu W, Shu H, Fang J, Yao M, Gu J, Cong W, Qin W.
Title LIFR functions as a metastasis suppressor in hepatocellular carcinoma by negatively regulating phosphoinositide 3-kinase/AKT pathway.
Journal Carcinogenesis
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.
Volume 36(10)
Pages 1201-12
Published 2015-10
DOI 10.1093/carcin/bgv108
PII bgv108
PMID 26249360
MeSH Adult Aged Biomarkers, Tumor Carcinoma, Hepatocellular / genetics* Carcinoma, Hepatocellular / pathology Female Gene Expression Regulation, Neoplastic Humans Janus Kinase 1 / metabolism Leukemia Inhibitory Factor Receptor alpha Subunit / biosynthesis* Leukemia Inhibitory Factor Receptor alpha Subunit / genetics Liver Neoplasms / genetics* Liver Neoplasms / pathology Male Matrix Metalloproteinase 13 / biosynthesis* Middle Aged Neoplasm Metastasis Oncogene Protein v-akt / genetics* Oncogene Protein v-akt / metabolism Phosphatidylinositol 3-Kinases / genetics Phosphorylation Prognosis Signal Transduction
IF 4.004
Times Cited 7
Human and Animal Cells