dc.creator | Martín Pérez, Rosa | es |
dc.creator | Yerbes, Rosario | es |
dc.creator | Mora Molina, Rocío | es |
dc.creator | Cano González, Ana María | es |
dc.creator | Arribas, Joaquín | es |
dc.creator | Mazzone, Massimiliano | es |
dc.creator | López Rivas, Abelardo | es |
dc.creator | Palacios, Carmen | es |
dc.date.accessioned | 2018-12-11T10:17:40Z | |
dc.date.available | 2018-12-11T10:17:40Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Martín Pérez, R., Yerbes, R., Mora Molina, R., Cano González, A.M., Arribas, J., Mazzone, M.,...,Palacios, C. (2017). Oncogenic p95HER2/611CTF primes human breast epithelial cells for metabolic stress-induced down-regulation of FLIP and activation of TRAIL-R/Caspase-8-dependent apoptosis. Oncotarget, 8 (55), 93688-93703. | |
dc.identifier.issn | 1949-2553 (electrónico) | es |
dc.identifier.uri | https://hdl.handle.net/11441/80929 | |
dc.description.abstract | Oncogenic transformation triggers reprogramming of cell metabolism, as part of
the tumorigenic process. However, metabolic reprogramming may also increase the
sensitivity of transformed cells to microenvironmental stress, at the early stages of
tumor development. Herein, we show that transformation of human breast epithelial
cells by the p95HER2/611CTF oncogene markedly sensitizes these cells to metabolic
stress induced by the simultaneous inhibition of glucose and glutamine metabolism.
In p95HER2/611CTF-transformed cells, metabolic stress activates a TNF related
apoptosis-inducing ligand (TRAIL)-R and caspase-8-dependent apoptotic process
that requires prior down-regulation of cellular FLICE-like inhibitor protein (c-FLIP)
levels. Importantly, sustained mTOR activation is involved in FLIP down-regulation
and apoptosis induced by metabolic stress. In vivo experiments in immunodeficient
mice demonstrate a requirement for caspase-8 in restraining primary tumor growth
of xenografts with p95HER2/611CTF-transformed cells. Collectively, these data define
a critical role of the extrinsic pathway of apoptosis in the control of tumor initiation
by microenvironmental cues. | es |
dc.description.sponsorship | Ministerio de Economía y Competitividad SAF2012-32824, SAF2015-64383-P | es |
dc.description.sponsorship | Junta de Andalucía BIO 778, CIBERONC ISCIII CB16/12/00421 | es |
dc.description.sponsorship | Red Temática de Investigación Cooperativa en Cáncer RD12/0036/0026, RD12/0036/0042 | es |
dc.description.sponsorship | Comunidad Europea (FEDER) | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Impact Journals | es |
dc.relation.ispartof | Oncotarget, 8 (55), 93688-93703. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | p95HER2/611CTF | es |
dc.subject | metabolic stress | es |
dc.subject | TRAIL-R | es |
dc.subject | FLIP | es |
dc.subject | mTOR | es |
dc.title | Oncogenic p95HER2/611CTF primes human breast epithelial cells for metabolic stress-induced down-regulation of FLIP and activation of TRAIL-R/Caspase-8-dependent apoptosis | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/acceptedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.relation.projectID | SAF2012-32824 | es |
dc.relation.projectID | SAF2015-64383-P | es |
dc.relation.projectID | BIO 778 | es |
dc.relation.projectID | CIBERONC ISCIII CB16/12/00421 | es |
dc.relation.projectID | RD12/0036/0026 | es |
dc.relation.projectID | RD12/0036/0042 | es |
dc.relation.publisherversion | https://doi.org/10.18632/oncotarget.21458 | es |
dc.identifier.doi | 10.18632/oncotarget.21458 | es |
idus.format.extent | 21 p. | es |
dc.journaltitle | Oncotarget | es |
dc.publication.volumen | 8 | es |
dc.publication.issue | 55 | es |
dc.publication.initialPage | 93688 | es |
dc.publication.endPage | 93703 | es |