SH3-domain binding protein 1 in the tumor microenvironment promotes hepatocellular carcinoma metastasis through WAVE2 pathway
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Yiming Tao1, Kuan Hu1, Fengbo Tan1, Sai Zhang2, Ming Zhou3, Jia Luo4 and Zhiming Wang1
1 Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China
2 Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, China
3 Institute of Cancer Research, Central South University, Changsha, Hunan, China
4 Department of Hepatobiliary Surgery, Hunan Provincial Tumor Hospital, Changsha, Hunan, China
Zhiming Wang, email:
Keywords: hepatocellular carcinoma, SH3-domain binding protein 1, Wiskott-Aldrich syndrome family verproline-homologous protein 2, metastasis, prognosis
Received: July 11, 2015 Accepted: February 11, 2016 Published: February 28, 2016
SH3-domain binding protein-1 (SH3BP1) specifically inactivating Rac1 and its target WAVE2 is required for cell motility. The present study shows SH3BP1 expression patterns in human HCC tissues and cell lines were examined. The regulation of SH3BP1 on HCC cell migration and invasion related to Rac1-WAVE2 signaling was characterized using in vitro and in vivo models. SH3BP1 overexpressed in HCC tissues and highly metastatic HCC cells was significantly associated vascular invasion (VI). SH3BP1 promoted VEGF secretion via Rac1-WAVE2 signaling, so as to exert an augmentation on cell invasion and microvessel formation. In three study cohorts with a total of 516 HCC patients, high SH3BP1 expression combined with high microvessel density (MVD) was confirmed as a powerful independent predictor of HCC prognosis in both training cohorts and validation cohort. Being an important angiogenic factor of HCC through Rac1-WAVE2 signaling, SH3BP1 promotes tumor invasion and microvessel formation contributing to HCC metastasis and recurrence. SH3BP1 is a novel WAVE2 regulator, a prognostic marker and a potential therapeutic target of HCC.
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