Oncogenic H-Ras and PI3K signaling can inhibit E-cadherin-dependent apoptosis and promote cell survival after photodynamic therapy in mouse keratinocytes
✍ Scribed by Jesús Espada; Sergio Galaz; Francisco Sanz-Rodríguez; Alfonso Blázquez-Castro; Juan Carlos Stockert; Lorea Bagazgoitia; Pedro Jaén; Salvador González; Amparo Cano; Ángeles Juarranz
- Publisher
- John Wiley and Sons
- Year
- 2009
- Tongue
- English
- Weight
- 345 KB
- Volume
- 219
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
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 p110α catalytic subunit of class IA PI3K. This protective effect is associated with β‐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 p110α. 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. J. Cell. Physiol. 219: 84–93, 2009. © 2008 Wiley‐Liss, Inc.