title: Disrupted interaction between CFTR and AF-6/afadin aggravates malignant phenotypes of colon cancer.
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.
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Cheng
authors.forename: Hu Zhang
authors.initials: HZ
authors.lastname: Xiao
authors.forename: Juan Juan
authors.initials: JJ
authors.lastname: Xiang
authors.forename: Jie Ting
authors.initials: JT
authors.lastname: Zhang
authors.forename: Siu Bun Sydney
authors.initials: SB
authors.lastname: Yu
authors.forename: Tracey Amanda
authors.initials: TA
authors.lastname: Martin
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.forename: Lai Ling
authors.initials: LL
authors.lastname: Tsang
authors.forename: Wen Guo
authors.initials: WG
authors.lastname: Jiang
authors.forename: Jiang
authors.initials: J
authors.lastname: Xiaohua
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism; D009218:Myosins / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D019108:Tight Junctions / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: C095516:AFDN protein, human; C505032:CFTR protein, human; D008840:Microfilament Proteins; C108835:afadin; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D020929:Mitogen-Activated Protein Kinase Kinases; D009218:Myosins; D016547:Kinesins