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01-01-2017 | Research Paper

Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity

Authors: Cunzhen Zhang, Fenghua Liu, Haiyang Chen, Nan Li, Zaili Luo, Weixing Guo, Dandan Huang, Shanhua Tang, Honggang Wang, Shuqun Cheng, Zhong Li, Hongyang Wang

Published in: Clinical & Experimental Metastasis | Issue 1/2017

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.

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Title: Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity
Authors: Cunzhen Zhang
Fenghua Liu
Haiyang Chen
Nan Li
Zaili Luo
Weixing Guo
Dandan Huang
Shanhua Tang
Honggang Wang
Shuqun Cheng
Zhong Li
Hongyang Wang
Publication date: 01-01-2017
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 1/2017
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-016-9825-7

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