Disrupted interaction between CFTR and AF-6/afadin aggravates malignant phenotypes of colon cancer

Sun, Ting Ting, Wang, Yan, Cheng, Hong, Zhang, Xiao Hu, Xiang, Juan Juan, Zhang, Jie Ting, Yu, Siu Bun Sydney, Martin, Tracey Amanda ORCID: https://orcid.org/0000-0003-2690-4908, Ye, Lin ORCID: https://orcid.org/0000-0002-0303-2409, Tsang, Lai Ling, Jiang, Wen Guo ORCID: https://orcid.org/0000-0002-3283-1111, Jiang, Xiaohua and Chan, Hsiao Chang 2014. Disrupted interaction between CFTR and AF-6/afadin aggravates malignant phenotypes of colon cancer. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1843 (3) , pp. 618-628. 10.1016/j.bbamcr.2013.12.013

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Abstract

How mutations or dysfunction of CFTR may increase the risk of malignancies in various tissues remains an open question. Here we report the interaction between CFTR and an adherens junction molecule, AF-6/afadin, and its involvement in the development of colon cancer. We have found that CFTR and AF-6/afadin are co-localized at the cell–cell contacts and physically interact with each other in colon cancer cell lines. Knockdown of CFTR results in reduced epithelial tightness and enhanced malignancies, with increased degradation and reduced stability of AF-6/afadin protein. The enhanced invasive phenotype of CFTR-knockdown cells can be completely reversed by either AF-6/afadin over-expression or ERK inhibitor, indicating the involvement of AF-6/MAPK pathway. More interestingly, the expression levels of CFTR and AF-6/afadin are significantly downregulated in human colon cancer tissues and lower expression of CFTR and/or AF-6/afadin is correlated with poor prognosis of colon cancer patients. The present study has revealed a previously unrecognized interaction between CFTR and AF-6/afadin that is involved in the pathogenesis of colon cancer and indicated the potential of the two as novel markers of metastasis and prognostic predictors for human colon cancer.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	CFTR; AF-6/afadin; Adherens junction; Colon cancer; Metastasis
Publisher:	Elsevier
ISSN:	0167-4889
Date of Acceptance:	16 December 2013
Last Modified:	16 Nov 2022 07:28
URI:	https://orca.cardiff.ac.uk/id/eprint/75807

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