Oncogenic H-Ras and PI3K signaling can inhibit E-cadherin-dependent apoptosis and promote cell survival after photodynamic therapy in mouse keratinocytes.

Maintenance of E-cadherin mediated cell-cell contacts is often required for the survival of epithelial cells and tissues. Here we report that oncogenic activation of H-Ras in murine keratinocytes can prevent cell death induced by immunological disruption of E-cadherin adhesion. A similar situation was observed in cells showing constitutive activation of the p110 alpha catalytic subunit of class IA PI3K. This protective effect is associated with beta-catenin-dependent transcription and with activation of survival factor Akt/PKB. In addition, we induced cell death by employing photodynamic therapy, using Zn-phthalocyanine as a photosensitizer that targets E-cadherin adhesion complexes. We have found that cell death based on this photodynamic action is also bypassed in cells showing constitutive activation of H-Ras and p110 alpha. Taken together, these results indicate that H-Ras/PI3K/Akt signaling plays a key role in cell survival mediated by E-cadherin cell-cell contacts.