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

被引：62

作者：

Luo, Qin ^{[1
]}

Wang, Cun ^{[1
]}

Jin, Guangzhi ^{[2
]}

Gu, Dishui ^{[1
]}

Wang, Ning ^{[1
]}

Song, Jin ^{[1
]}

Jin, Haojie ^{[1
]}

Hu, Fangyuan ^{[1
]}

Zhang, Yurong ^{[1
]}

Ge, Tianxiang ^{[1
]}

Huo, Xisong ^{[1
]}

Chu, Wei ^{[1
]}

Shu, Huiqun ^{[1
]}

Fang, Jingyuan ^{[1
]}

Yao, Ming ^{[1
]}

Gu, Jianren ^{[1
]}

Cong, Wenming ^{[2
]}

Qin, Wenxin ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Renji Hosp, Sch Med, Shanghai Canc Inst,State Key Lab Oncogenes & Rela, Shanghai 200032, Peoples R China

[2] Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Pathol, Shanghai 200438, Peoples R China

来源：

CARCINOGENESIS | 2015年 / 36卷 / 10期

基金：

中国国家自然科学基金; 高等学校博士学科点专项科研基金;

关键词：

INHIBITORY FACTOR-RECEPTOR; IL-6 SIGNAL TRANSDUCER; KINASE JAK1; CANCER; ASSOCIATION; ACTIVATION; EXPRESSION; MIGRATION; CYTOKINES; CELLS;

D O I：

10.1093/carcin/bgv108

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：1201 / 1212

页数：12

共 32 条

[1] DNA methylation controls the responsiveness of hepatoma cells to leukemia inhibitory factor [J].