Caveolae mediate growth factor-induced disassembly of adherens junctions to support tumor cell dissociation

Lidiya Orlichenko, Shaun G. Weller, Cao Hong, Eugene W. Krueger, Muyiwa Awoniyi, Galina Beznoussenko, Roberto Buccione, Mark A. McNiven

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Remodeling of cell-cell contacts through the internalization of adherens junction proteins is an important event during both normal development and the process of tumor cell metastasis. Here we show that the integrity of tumor cell-cell contacts is disrupted after epidermal growth factor (EGF) stimulation through caveolae-mediated endocytosis of the adherens junction protein E-cadherin. Caveolin-1 and E-cadherin closely associated at cell borders and in internalized structures upon stimulation with EGF. Furthermore, preventing caveolae assembly through reduction of caveolin-1 protein or expression of a caveolin-1 tyrosine phospho-mutant resulted in the accumulation of E-cadherin at cell borders and the formation of tightly adherent cells. Most striking was the fact that exogenous expression of caveolin-1 in tumor cells that contain tight, well-defined, borders resulted in a dramatic dispersal of these cells. Together, these findings provide new insights into how cells might disassemble cell-cell contacts to help mediate the remodeling of adherens junctions, and tumor cell metastasis and invasion.

Original languageEnglish (US)
Pages (from-to)4140-4152
Number of pages13
JournalMolecular biology of the cell
Volume20
Issue number19
DOIs
StatePublished - Oct 1 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Orlichenko, L., Weller, S. G., Hong, C., Krueger, E. W., Awoniyi, M., Beznoussenko, G., Buccione, R., & McNiven, M. A. (2009). Caveolae mediate growth factor-induced disassembly of adherens junctions to support tumor cell dissociation. Molecular biology of the cell, 20(19), 4140-4152. https://doi.org/10.1091/mbc.E08-10-1043