Hepatitis B Virus X Protein Induces RHAMM-Dependent Motility in Hepatocellular Carcinoma Cells via PI3K-AktOct-1 Signaling

被引：16

作者：

Liu, Yu-Chin ^{[1
]}

Lu, Li-Feng ^{[1
]}

Li, Chia-Jung ^{[1
]}

Sun, Nian-Kang ^{[2
,3
]}

Guo, Jing-You ^{[4
]}

Huang, Ya-Hui ^{[5
]}

Chiu, Cheng-Tang ^{[5
]}

Chao, Chuck C-K ^{[1
,2
,5
]}

机构：

[1] Chang Gung Univ, Coll Med, Grad Inst Biomed Sci, Taoyuan, Taiwan

[2] Chang Gung Univ, Coll Med, Dept Biochem & Mol Biol, Taoyuan, Taiwan

[3] Chang Gung Univ Sci & Technol, Div Biomed Sci, Taoyuan, Taiwan

[4] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

[5] Chang Gung Mem Hosp, Liver Res Ctr, Linkou Branch, Taoyuan, Taiwan

来源：

MOLECULAR CANCER RESEARCH | 2020年 / 18卷 / 03期

关键词：

SENSITIZES CANCER-CELLS; UP-REGULATION; REGULATED EXPRESSION; ANDROGEN RECEPTOR; ANTIGEN EFFECTOR; GROWTH; GENE; METASTASIS; APOPTOSIS; INSTABILITY;

D O I：

10.1158/1541-7786.MCR-19-0463

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC), which represents one of the most common cancers worldwide. Recent studies suggest that HBV's protein X (HBx) plays a crucial role in HCC development and progression. Earlier, genome-wide analysis identified that the receptor for hyaluronan-mediated motility (RHAMM) represents a putative oncogene and is overexpressed in many human cancers, including HCC. However, the mechanism underlying RHAMM upregulation and its role in tumorigenesis remain unclear. Here, we show that ectopic expression of HBx activates the PI3K/Akt/Oct-1 pathway and upregulates RHAMM expression in HCC cells. HBx overexpression leads to dissociation of C/EBPb from the RHAMM gene promoter, thereby inducing RHAMM upregulation. RHAMM knockdown attenuates HBx-induced cell migration and invasion in vitro. In mice, HBx promotes cancer cell colonization via RHAMM upregulation, resulting in enhanced metastasis. Analysis of gene expression datasets reveals that RHAMM mRNA level is upregulated in patients with HCC with poor prognosis.

引用

页码：375 / 389

页数：15

共 41 条

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