Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity
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- 作者：Cunzhen Zhang ; Fenghua Liu ; Haiyang Chen ; Nan Li…
- 关键词：HCC ; Bif ; 1 ; Metastasis ; Cdc42
- 刊名：Clinical & Experimental Metastasis
- 出版年：2017
- 出版时间：January 2017
- 年：2017
- 卷：34
- 期：1
- 页码：11-23
- 全文大小：
- 刊物主题：Cancer Research; Biomedicine, general; Oncology; Hematology; Surgical Oncology;
- 出版者：Springer Netherlands
- ISSN：1573-7276
- 卷排序：34
文摘
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.