title: Caveolin-1 regulates Mcl-1 stability and anoikis in lung carcinoma cells.
abstract: Both caveolin-1 (Cav-1) and Mcl-1 have been implicated in the regulation of cancer cell anoikis, but their relationship and underlying mechanisms of regulation are not known. The present study demonstrated for the first time that Cav-1 regulates Mcl-1 through protein-protein interaction and inhibits its downregulation during cell anoikis in human lung cancer cells. Immunoprecipitation and immunocytochemistry studies showed that Cav-1 interacted with Mcl-1 and prevented it from degradation via the ubiquitin-proteasome pathway. Mcl-1 and Mcl-1-Cav-1 complex were highly elevated in Cav-1-overexpressing cells but were greatly reduced in Cav-1 knockdown cells. Consistent with this finding, we found that Mcl-1 ubiquitination was significantly attenuated by Cav-1 overexpression but increased by Cav-1 knockdown. Together, our results indicate a novel role of Cav-1 in anoikis regulation through Mcl-1 interaction and stabilization, which provides a new insight to the pathogenesis of metastatic lung cancer and its potential treatment.
authors.affiliation: Pharmaceutical Technology (International) Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Preedakorn
authors.initials: P
authors.lastname: Chunhacha
authors.forename: Varisa
authors.initials: V
authors.lastname: Pongrakhananon
authors.forename: Yon
authors.initials: Y
authors.lastname: Rojanasakul
authors.forename: Pithi
authors.initials: P
authors.lastname: Chanvorachote
mesh_terms: D023102:Anoikis / Q000502:physiology*; D015153:Blotting, Western; D051242:Caveolin 1 / Q000378:metabolism*; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051242:Caveolin 1; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2