Rac-dependent cyclin D1 gene expression regulated by cadherin- and integrin-mediated adhesion.

TitleRac-dependent cyclin D1 gene expression regulated by cadherin- and integrin-mediated adhesion.
Publication TypeJournal Article
Year of Publication2008
AuthorsFournier AK, Campbell LE, Castagnino P, Liu WF, Chung BM, Weaver VM, Chen CS, Assoian RK
JournalJ Cell Sci
Volume121
IssuePt 2
Pagination226-33
Date Published2008 Jan 15
ISSN0021-9533
KeywordsCadherins, Cell Adhesion, Cell Communication, Cell Line, Tumor, Cyclin D1, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, Gene Expression Regulation, Gene Expression Regulation, Neoplastic, Humans, Integrins, Models, Biological, rac GTP-Binding Proteins, Signal Transduction
Abstract

Integrin-mediated adhesion to substratum is required for cyclin D1 induction in mesenchymal cells, but we show here that the induction of cyclin D1 persists despite blockade of ECM-integrin signaling in MCF10A mammary epithelial cells. E-cadherin-mediated cell-cell adhesion also supports cyclin D1 induction in these cells, and the combined inhibition of both E-cadherin and integrin adhesion is required to prevent the expression of cyclin D1 mRNA and protein. Our previous studies described a pro-proliferative effect of E-cadherin in MCF10A cells, mediated by Rac, and we now show that Rac is required for cyclin D1 mRNA induction by both E-cadherin and integrin engagement. The levels of p21Cip1 and p27Kip1, Cdk inhibitors that are also targets of integrin signaling, are not affected by E-cadherin-mediated cell-cell adhesion. Finally, we show that the increased expression of cyclin D1 mRNA associated with E-cadherin-dependent cell-cell adhesion is causally linked to an increased entry into S phase. Our results identify Rac signaling to cyclin D1 as a crucial pro-proliferative effect of E-cadherin-mediated cell-cell adhesion.

DOI10.1242/jcs.017012
Alternate JournalJ. Cell. Sci.
PubMed ID18187454
PubMed Central IDPMC2662746
Grant ListCA078731 / CA / NCI NIH HHS / United States
CA72639 / CA / NCI NIH HHS / United States
HL73305 / HL / NHLBI NIH HHS / United States
R01 CA078731-07 / CA / NCI NIH HHS / United States
R25-CA-101871 / CA / NCI NIH HHS / United States