TY - JOUR
T1 - Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity
AU - Zhang, Cunzhen
AU - Liu, Fenghua
AU - Chen, Haiyang
AU - Li, Nan
AU - Luo, Zaili
AU - Guo, Weixing
AU - Huang, Dandan
AU - Tang, Shanhua
AU - Wang, Honggang
AU - Cheng, Shuqun
AU - Li, Zhong
AU - Wang, Hongyang
N1 - Funding Information:
We thank Huanlin Sun, Dongping Hu, Liang Tang, LinnaGuo, and Shanna Huang for their technical assistance. This work was supported by Grants from the National Natural Science Foundation of China (81221061, 81272427 and 31471339); The Ministry of Science and Technology Key Program (2012ZX10002-009, -011); The State Key Project on Diseases of China (2012zx10002016016003); The China National Funds for Distinguished Young Scientists (81125018); the Chang Jiang Scholars Program (2013) of the China Ministry of Education; and The National Key Basic Research Program “973 project” (2015CB554000).
Publisher Copyright:
© 2016, Springer Science+Business Media Dordrecht.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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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U2 - 10.1007/s10585-016-9825-7
DO - 10.1007/s10585-016-9825-7
M3 - Article
C2 - 27730394
AN - SCOPUS:84991071434
VL - 34
SP - 11
EP - 23
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
SN - 0262-0898
IS - 1
ER -
