title: Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity.
abstract: Tumor metastasis is the process by which tumor cells disseminate from tumors and enter nearby and distant microenvironments for new colonization. Bif-1 (BAX-interacting factor 1), which has a BAR domain and an SH3 domain, has been reported to be involved in cell growth, apoptosis and autophagy. However, the influence of Bif-1 on metastasis has been less studied. To understand the role of Bif-1 in metastasis, we studied the expression levels of Bif-1 in human HCC specimens using immunohistochemistry, a tissue microarray and quantitative PCR. The function of Bif-1 was assessed in migration and translocation assays and the pulmonary metastatic animal model. The relationship between Bif-1 and the Rho family was determined using immunoblot analyses and chromatin immunoprecipitation. The results showed that the expression of Bif-1 was higher in hepatocellular carcinoma (HCC) than matched adjacent non-tumor liver tissues. Increased Bif-1 expression was associated with tumor size and the intercellular spread and metastasis of HCC. Analysis of the relationship between Bif-1 expression and patients' clinical characteristics revealed that patients with higher levels of Bif-1 had shorter disease-free and overall survival rates. Knockdown of Bif-1 with RNAi suppressed the migration of HCC cells and pulmonary metastasis and decreased the expression of Cdc42, a member of the Rho family. Bif-1 localized to the cytosol and nucleus and interacted with the promoter transcription region of Cdc42, which may regulate Cdc42 expression. Our results demonstrate a novel role of Bif-1 in HCC, in which Bif-1 promotes cell metastasis by regulating Cdc42 expression and activity.
authors.affiliation: Department of Surgery, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, Shanghai, China.|International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China.
authors.forename: Cunzhen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Central Laboratory, The 10th People's Hospital, Tongji University, Shanghai, China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Liu
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Surgery, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China.
authors.forename: Zaili
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Surgery, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, Shanghai, China.
authors.forename: Weixing
authors.initials: W
authors.lastname: Guo
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Huang
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China.
authors.forename: Shanhua
authors.initials: S
authors.lastname: Tang
authors.affiliation: Department of Pharmacology, Penn State University College of Medicine, Hershey, PA, USA.
authors.forename: Honggang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Surgery, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, Shanghai, China. chengshuqun@aliyun.com.
authors.forename: Shuqun
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology, Central Laboratory, The 10th People's Hospital, Tongji University, Shanghai, China. lizhongsh@yahoo.com.|Shanghai Cell Therapy Research Institute, 75 Qianyang Road, Shanghai, China. lizhongsh@yahoo.com.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.affiliation: International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, The Second Military Medical University, 225 Changhai Road, Shanghai, China. hywangk@vip.sina.com.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D008297:Male; D051379:Mice; D008875:Middle Aged; D009362:Neoplasm Metastasis; D023041:Xenograft Model Antitumor Assays; D020764:cdc42 GTP-Binding Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C429293:SH3GLB1 protein, human; D020764:cdc42 GTP-Binding Protein
keywords: Bif-1; Cdc42; HCC; Metastasis