title: SH3-domain binding protein 1 in the tumor microenvironment promotes hepatocellular carcinoma metastasis through WAVE2 pathway.
abstract: 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.
authors.affiliation: Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Kuan
authors.initials: K
authors.lastname: Hu
authors.affiliation: Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Fengbo
authors.initials: F
authors.lastname: Tan
authors.affiliation: Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Sai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Institute of Cancer Research, Central South University, Changsha, Hunan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Hepatobiliary Surgery, Hunan Provincial Tumor Hospital, Changsha, Hunan, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004265:DNA Helicases; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009362:Neoplasm Metastasis; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D015398:Signal Transduction; D059016:Tumor Microenvironment; D051300:Wiskott-Aldrich Syndrome Protein Family / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; C107953:RAC1 protein, human; D000067776:RNA Recognition Motif Proteins; C120152:WASF2 protein, human; D051300:Wiskott-Aldrich Syndrome Protein Family; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases; D020830:rac1 GTP-Binding Protein
keywords: SH3-domain binding protein 1; Wiskott-Aldrich syndrome family verproline-homologous protein 2; hepatocellular carcinoma; metastasis; prognosis