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Cross-talk between Her2/ERBB2 signaling and the unfolded protein response in the regulation of apoptosis: Activation of the TRAIL system

AuthorsMartín-Pérez, Rosa ; Palacios, Carmen ; Yerbes, Rosario ; Cano-González, Ana ; López-Rivas, Abelardo
Issue Date30-Mar-2014
Citation9th European Workshops on Cell Death (2014)
AbstractERBB2/HER2/Neu is a transmembrane receptor of the ERBB family of proteins with tyrosine kinase activity that is overexpressed in approximately 20% of human breast tumors. Truncated or mutant forms of ERBB2 with constitutively active kinase activity have been found in a number of breast tumors and show an increased oncogenicity compared with wild-type ERBB2. We have found that human breast epithelial cells that express a constitutively active ERBB2 are very sensitive to agents inducing endoplasmic reticulum (ER) stress. Our results show that expression of the activated ERBB2 oncogene leads to alterations in the unfolded protein response (UPR) of these cells upon ER stress. Our results also demonstrate that deregulation of the ERK, AKT and mTOR activities in mutant ERBB2-expressing cells is involved in the differential response of the UPR to ER stress agents and the resulting cell death. Finally, our data clearly indicate that the increased sensitivity of mutant ERBB2-expressing cells to ER stress is dependent on the activation of the PERK/ATF4/CHOP branch of the UPR. Collectively, these data revealed the potential therapeutic use of treatments inducing ER stress against breast tumor cells expressing constitutively active forms of ERBB2
DescriptionTrabajo presentado en el 9th European Workshops on Cell Death: Death with Aphrodite, celebrado en Paphos (Cyprus) del 30 de marzo al 3 de abril de 2014
Appears in Collections:(CABIMER) Comunicaciones congresos
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