@article {411, title = {Rac-dependent cyclin D1 gene expression regulated by cadherin- and integrin-mediated adhesion.}, journal = {J Cell Sci}, volume = {121}, year = {2008}, month = {2008 Jan 15}, pages = {226-33}, 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.

}, keywords = {Cadherins, 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}, issn = {0021-9533}, doi = {10.1242/jcs.017012}, author = {Fournier, Alaina K and Campbell, Latoya E and Castagnino, Paola and Liu, Wendy F and Chung, Betty M and Weaver, Valerie M and Chen, Christopher S and Assoian, Richard K} }