title: p53 controls colorectal cancer cell invasion by inhibiting the NF-κB-mediated activation of Fascin.
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.
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.|Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Xinbing
authors.initials: X
authors.lastname: Sui
authors.affiliation: Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, China.|Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Haimei
authors.initials: H
authors.lastname: Tang
authors.affiliation: Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Jichun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.|Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.|Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Da
authors.initials: D
authors.lastname: Li
authors.affiliation: Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal Surgery, Nankai Hospital, Nankai District, Tianjin, China.
authors.forename: Junhong
authors.initials: J
authors.lastname: Ma
authors.affiliation: Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Jing
authors.affiliation: Department of Breast Surgery, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
authors.forename: Xidong
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.|Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Pan
authors.affiliation: Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang, China.|Department of Colorectal Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Chao
authors.initials: C
authors.lastname: He
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D015398:Signal Transduction; D015996:Survival Rate; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D008840:Microfilament Proteins; D016328:NF-kappa B; C495901:TP53 protein, human; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53; C020324:fascin
keywords: Fascin; NF-κB; cancer; cell invasion; p53