Oncotarget

Research Papers:

p53 controls colorectal cancer cell invasion by inhibiting the NF-κB-mediated activation of Fascin

Xinbing Sui _, Jing Zhu, Haimei Tang, Chan Wang, Jichun Zhou, Weidong Han, Xian Wang, Yong Fang, Yinghua Xu, Da Li, Rui Chen, Junhong Ma, Zhao Jing, Xidong Gu, Hongming Pan and Chao He

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Oncotarget. 2015; 6:22869-22879. https://doi.org/10.18632/oncotarget.5137

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Abstract

Xinbing Sui1,2,*, Jing Zhu2,3,*, Haimei Tang2, Chan Wang2, Jichun Zhou4, Weidong Han1,2, Xian Wang1,2, Yong Fang1, Yinghua Xu1, Da Li1, Rui Chen2, Junhong Ma6, Zhao Jing2, Xidong Gu5, Hongming Pan1,2, Chao He2,3

1Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China

2Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, China

3Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China

4Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China

5Department of Breast Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China

6Department of Gastrointestinal Surgery, Nankai Hospital, Nankai District, Tianjin, China

*These authors have contributed equally to this work

Correspondence to:

Hongming Pan, e-mail: drpanhm@aliyun.com

Chao He, e-mail: hechao@163.com

Xinbing Sui, e-mail: hzzju@zju.edu.cn

Keywords: p53, cancer, cell invasion, NF-κB, Fascin

Received: June 05, 2015     Accepted: August 20, 2015     Published: September 01, 2015

ABSTRACT

p53 mutation is known to contribute to cancer progression. Fascin is an actin-bundling protein and has been recently identified to promote cancer cell migration and invasion through its role in formation of cellular protrusions such as filopodia and invadopodia. However, the relationship between p53 and Fascin is not understood. Here, we have found a new link between them. In colorectal adenocarcinomas, p53 mutation correlated with high NF-κB, Fascin and low E-cadherin expression. Moreover, this expression profile was shown to contribute to poor overall survival in patients with colorectal cancer. Wild-type p53 could inhibit NF-κB activity that repressed the expression of Fascin and cancer cell invasiveness. In contrast, in p53-deficient primary cultured cells, NF-κB activity was enhanced and then activation of NF-κB increased the expression of Fascin. In further analysis, we showed that NF-κB was a key determinant for p53 deletion-stimulated Fascin expression. Inhibition of NF-κB/p65 expression by pharmacological compound or p65 siRNA suppressed Fascin activity in p53-deficient cells. Moreover, restoration of p53 expression decreased the activation of Fascin through suppression of the NF-κB pathway. Taken together, these data suggest that a negative-feedback loop exists, whereby p53 can suppress colorectal cancer cell invasion by inhibiting the NF-κB-mediated activation of Fascin.


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