Editors' ChoiceApoptosis

Cadherins Regulate Cell Survival

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Science's STKE  10 Sep 2002:
Vol. 2002, Issue 149, pp. tw333-TW333
DOI: 10.1126/stke.2002.149.tw333

Cell-matrix and cell-cell adhesions are important regulators of cell survival. Modulation of either can result in tumor formation and metastasis. The former is regulated by cell-surface integrins, whereas contact between adjacent cells is mediated by cell-surface cadherins. How cadherins control cell survival has not been clear. Increased expression of N-cadherin has been associated with increased invasiveness and cell survival of some carcinomas. Tran et al. report that this may be due stabilization of the antiapoptotic protein Bcl-2. In the absence of integrin-mediated adhesion and growth factors, prostate carcinoma cells in suspension suppressed cell death. This was dependent on cell-cell adhesion through N-cadherin and correlated with increased activation of phosphatidylinositol 3-kinase and the serine-threonine kinase Akt. Intercellular adhesion also induced increased Bcl-2 expression. The survival pathway initiated by integrins also converges on Akt, which suggests overlap between the two adhesion-dependent pathways.

N. L. Tran, D. G. Adams, R. R. Vaillancourt, R. L. Heimark, Signal transduction from N-cadherin increases Bcl-2. J. Biol. Chem. 277, 32905-32914 (2002). [Abstract] [Full Text]