| First Author | Tran NL | Year | 2002 |
| Journal | J Biol Chem | Volume | 277 |
| Issue | 36 | Pages | 32905-14 |
| PubMed ID | 12095980 | Mgi Jnum | J:78826 |
| Mgi Id | MGI:2386348 | Doi | 10.1074/jbc.M200300200 |
| Citation | Tran NL, et al. (2002) Signal Transduction from N-cadherin Increases Bcl-2. REGULATION OF THE PHOSPHATIDYLINOSITOL 3-KINASE/Akt PATHWAY BY HOMOPHILIC ADHESION AND ACTIN CYTOSKELETAL ORGANIZATION. J Biol Chem 277(36):32905-14 |
| abstractText | Associated with the metastatic progression of epithelial tumors is the dynamic regulation of cadherins. Whereas E-cadherin is expressed in most epithelium and carcinomas, recent studies suggest that the up-regulation of other cadherin subtypes in carcinomas, such as N-cadherin, may function in cancer progression. We demonstrate that a signal transduction cascade links the N-cadherin.catenin adhesion complex to up-regulation of the anti-apoptotic protein Bcl-2. In suspension, aggregates of DU-145 cells, an E-cadherin expressing human prostate carcinoma line, survive loss of integrin-dependent adhesion by a different anti-apoptotic signaling pathway than the N-cadherin expressing lines PC3 and PC3N. N-cadherin intercellular adhesion mediates a 3.5-fold increase in Bcl-2 protein expression, whereas the level of the proapoptotic protein Bax remains constant. Only N-cadherin ligation in PC3 cells, which express both N-cadherin and E-cadherin, is sufficient to induce activation of Akt/protein kinase B. N-cadherin homophilic ligation initiates phosphatidylinositol 3-kinase-dependent activation of Akt resulting in Akt phosphorylation of Bad on serine 136. Following N-cadherin homophilic adhesion phosphatidylinositol 3-kinase was identified in immunoprecipitates of the N-cadherin.catenin complex. The recruitment of phosphatidylinositol 3-kinase to the adhesion complex is dependent on ligation of N-cadherin and an organized actin cytoskeleton because cytochalasin D blocks the recruitment. We propose that N-cadherin homophilic adhesion can initiate anti-apoptotic signaling, which enhances the Akt cell survival pathway in metastatic cancer. |
