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.
Espada
Jesús
J
Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain. jespada@iib.uam.es
Galaz
Sergio
S
Sanz-Rodríguez
Francisco
F
Blázquez-Castro
Alfonso
A
Stockert
Juan Carlos
JC
Bagazgoitia
Lorea
L
Jaén
Pedro
P
González
Salvador
S
Cano
Amparo
A
Juarranz
Angeles
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology*; D004789:Enzyme Activation; D007211:Indoles / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism; D054833:Isoindoles; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010778:Photochemotherapy; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism*; D011838:Radiation-Sensitizing Agents / Q000378:metabolism; D015398:Signal Transduction
D015820:Cadherins; D007211:Indoles; D054833:Isoindoles; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D016283:Proto-Oncogene Proteins p21(ras); D011838:Radiation-Sensitizing Agents; C013647:phthalocyanine