Journal article
Activated ERBB2/Her2 licenses sensitivity to apoptosis upon endoplasmic reticulum stress through a PERK-dependent pathway
Cancer research (Chicago, Ill.), v 74(6), pp 1766-1777
15 Mar 2014
PMID: 24453000
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
HER2/Neu/ERBB2 is a receptor tyrosine kinase overexpressed in
approximately 20% of human breast tumors. Truncated or mutant isoforms
which show increased oncogenicity compared to the wild-type receptor are found
in many breast tumors. Here we report that constitutively active ERBB2
sensitizes human breast epithelial cells to agents that induce endoplasmic
reticulum (ER) stress, altering the unfolded protein response (UPR) of these
cells. Deregulation of the ERK, AKT and mTOR activities elicited by mutant ERBB2
were involved in mediating this differential UPR response, elevating the
response to ER stress and apoptotic cell death. Mechanistic investigations
revealed that the increased sensitivity of mutant ERBB2-expressing cells to ER
stress relied upon a UPR effector signaling involving the PERK-ATF4-CHOP
pathway, upregulation of the proapoptotic cell surface receptor TRAIL-R2 and
activation of proapoptotic caspase-8. Collectively, our results offer a
rationale for the therapeutic exploration of treatments inducing ER stress
against mutant ERBB2-expressing breast tumor cells.
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Details
- Title
- Activated ERBB2/Her2 licenses sensitivity to apoptosis upon endoplasmic reticulum stress through a PERK-dependent pathway
- Creators
- Rosa Martín-Pérez - Centro Andaluz de Biología Molecular y Medicina Regenerativa-CSIC, CABIMER, Avda Américo Vespucio s/n, 41092 Sevilla, SpainCarmen Palacios - Centro Andaluz de Biología Molecular y Medicina Regenerativa-CSIC, CABIMER, Avda Américo Vespucio s/n, 41092 Sevilla, SpainRosario Yerbes - Centro Andaluz de Biología Molecular y Medicina Regenerativa-CSIC, CABIMER, Avda Américo Vespucio s/n, 41092 Sevilla, SpainAna Cano-González - Centro Andaluz de Biología Molecular y Medicina Regenerativa-CSIC, CABIMER, Avda Américo Vespucio s/n, 41092 Sevilla, SpainDaniel Iglesias-Serret - Departament de Ciències Fisiològiques II, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL)-Universitat de Barcelona, L’Hospitalet de Llobregat, Barcelona, SpainJoan Gil - Departament de Ciències Fisiològiques II, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL)-Universitat de Barcelona, L’Hospitalet de Llobregat, Barcelona, SpainMauricio J Reginato - Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, USAAbelardo López-Rivas - Centro Andaluz de Biología Molecular y Medicina Regenerativa-CSIC, CABIMER, Avda Américo Vespucio s/n, 41092 Sevilla, Spain
- Publication Details
- Cancer research (Chicago, Ill.), v 74(6), pp 1766-1777
- Publisher
- American Association for Cancer Research (AACR)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000333811700015
- Scopus ID
- 2-s2.0-84896502656
- Other Identifier
- 991014877914504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology