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

Cunzhen Zhang, Fenghua Liu, Haiyang Chen, Nan Li, Zaili Luo, Weixing Guo, Dandan Huang, Shanhua Tang, Hong-Gang Wang, Shuqun Cheng, Zhong Li, Hongyang Wang

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)11-23
Number of pages13
JournalClinical and Experimental Metastasis
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2017

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Cell Movement
Hepatocellular Carcinoma
Neoplasm Metastasis
Neoplasms
Rho Factor
Lung
src Homology Domains
Chromatin Immunoprecipitation
Autophagy
RNA Interference
Genetic Promoter Regions
Cytosol
Disease-Free Survival
Survival Rate
Animal Models
Immunohistochemistry
Apoptosis
Polymerase Chain Reaction
Liver
Growth

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Zhang, Cunzhen ; Liu, Fenghua ; Chen, Haiyang ; Li, Nan ; Luo, Zaili ; Guo, Weixing ; Huang, Dandan ; Tang, Shanhua ; Wang, Hong-Gang ; Cheng, Shuqun ; Li, Zhong ; Wang, Hongyang. / Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity. In: Clinical and Experimental Metastasis. 2017 ; Vol. 34, No. 1. pp. 11-23.
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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.",
author = "Cunzhen Zhang and Fenghua Liu and Haiyang Chen and Nan Li and Zaili Luo and Weixing Guo and Dandan Huang and Shanhua Tang and Hong-Gang Wang and Shuqun Cheng and Zhong Li and Hongyang Wang",
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Zhang, C, Liu, F, Chen, H, Li, N, Luo, Z, Guo, W, Huang, D, Tang, S, Wang, H-G, Cheng, S, Li, Z & Wang, H 2017, 'Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity', Clinical and Experimental Metastasis, vol. 34, no. 1, pp. 11-23. https://doi.org/10.1007/s10585-016-9825-7

Bif-1 promotes tumor cell migration and metastasis via Cdc42 expression and activity. / Zhang, Cunzhen; Liu, Fenghua; Chen, Haiyang; Li, Nan; Luo, Zaili; Guo, Weixing; Huang, Dandan; Tang, Shanhua; Wang, Hong-Gang; Cheng, Shuqun; Li, Zhong; Wang, Hongyang.

In: Clinical and Experimental Metastasis, Vol. 34, No. 1, 01.01.2017, p. 11-23.

Research output: Contribution to journalArticle

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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, Hong-Gang

AU - Cheng, Shuqun

AU - Li, Zhong

AU - Wang, Hongyang

PY - 2017/1/1

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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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