Caveolae mediate growth factor-induced disassembly of adherens junctions to support tumor cell dissociation.
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.
Orlichenko
Lidiya
L
Mayo Clinic, Department of Biochemistry and Molecular Biology and the Miles and Shirley Fiterman Center for Digestive Diseases, Rochester, MN 55905, USA.
Weller
Shaun G
SG
Cao
Hong
H
Krueger
Eugene W
EW
Awoniyi
Muyiwa
M
Beznoussenko
Galina
G
Buccione
Roberto
R
McNiven
Mark A
MA
D022005:Adherens Junctions / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism* / Q000648:ultrastructure; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009154:Mutation; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects
C495540:CAV1 protein, human; D015820:Cadherins; D051242:Caveolin 1; D049452:Green Fluorescent Proteins; D004815:Epidermal Growth Factor