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Oncotarget. 2015 Sep 8;6(26):22869-79.

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

Sui X1,2, Zhu J2,3, Tang H2, Wang C2, Zhou J4, Han W1,2, Wang X1,2, Fang Y1, Xu Y1, Li D1, Chen R2, Ma J5, Jing Z2, Gu X6, Pan H1,2, He C2,3.

Author information

1
Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
2
Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, China.
3
Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
4
Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
5
Department of Gastrointestinal Surgery, Nankai Hospital, Nankai District, Tianjin, China.
6
Department of Breast Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

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.

KEYWORDS:

Fascin; NF-κB; cancer; cell invasion; p53

PMID:
26362504
PMCID:
PMC4673205
DOI:
10.18632/oncotarget.5137
[Indexed for MEDLINE]
Free PMC Article

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