Role of IQGAP3 in metastasis and epithelial–mesenchymal transition in human hepatocellular carcinoma

Journal of Translational Medicine

Research

Nan Qin¹  Bo Chen¹  Yongjie Shi¹  Sicong Huang¹  Hongyun Jia¹  Qiang Zhou¹  Yanqiu Chen²  Gang Shen³ 

[1] Department of Clinical Examination, The Second Affiliated Hospital of Guangzhou Medical University, 510260, Guangzhou, Guangdong, People’s Republic of China;Department of ENT, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9th Jinsui Road, 510623, Guangzhou, Guangdong, People’s Republic of China;Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, 9th Jinsui Road, 510623, Guangzhou, Guangdong, People’s Republic of China;

关键词: IQGAP3;    Hepatocellular carcinoma;    Metastasis;    Epithelial–mesenchymal transition;    TGF-β signaling;   

DOI  :  10.1186/s12967-017-1275-8

 received in 2017-05-08, accepted in 2017-08-01,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundHepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide owing to its high rates of metastasis and recurrence. The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is ubiquitously overexpressed in several human cancers, including liver, ovary, lung, large intestine, gastric, bone marrow, and breast malignancies and is involved in the invasion and metastasis of cancer cells. Therefore, we aimed to determine the biological role and molecular mechanism of IQGAP3 in HCC.MethodsWe used 120 archived clinical HCC samples, 9 snap-frozen HCC tumor tissues, and 4 normal liver tissues. Expression of IQGAP3 mRNA and protein in HCC cell lines (Hep3B, SMMC-7721, HCCC-9810, HepG2, BEL-7404, HCCLM3, QGY-7701, Huh7, and MHCC97H) and normal liver epithelial cells LO2 was examined by western blot, quantitative polymerase chain reaction, and immunohistochemistry. In addition, wound-healing and transwell matrix penetration assays were used to assess the migratory and invasive abilities of HCC cells, respectively.ResultsExpression of the IQGAP3 was robustly upregulated in HCC cells and tissues. High expression of IQGAP3 in HCC correlated with aggressive clinicopathological features and was an independent poor prognostic factor for overall survival. Furthermore, ectopic expression of IQGAP3 markedly enhanced HCC cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) in vitro and promoted metastasis of orthotopic hepatic tumors in nude mice. Conversely, silencing endogenous IQGAP3 showed an opposite effect. Mechanistically, IQGAP3 promoted EMT and metastasis by activating TGF-β signaling.ConclusionsIQGAP3 functions as an important regulator of metastasis and EMT by constitutively activating the TGF-β signaling pathway in HCC. Our findings present new evidence of the role of IQGAP3 in EMT and metastasis, indicating its potential as a prognostic biomarker candidate and a therapeutic target against HCC.

【 授权许可】

CC BY   
© The Author(s) 2017