Caveolin-1 Regulates Mcl-1 Stability and Anoikis in Lung Carcinoma Cells

Preedakorn Chunhacha, Varisa Pongrakhananon, Yon Rojanasakul, Pithi Chanvorachote

Research output: Contribution to journalArticle

35 Scopus citations

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 down regulation during cell anoikis in human lung cancer cells. Immunoprecipitation and immunocyto-chemistry 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 over expression 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.

Original languageEnglish (US)
Pages (from-to)C1284-C1292
JournalAmerican Journal of Physiology - Cell Physiology
Volume302
Issue number9
DOIs
StatePublished - May 1 2012

Keywords

  • Anoikis resistance
  • Lung cancer
  • Metastasis
  • Myeloid cell leukemia-1

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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