Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein response

Autores
Lacunza, Ezequiel; Rabassa, Martín Enrique; Canzoneri, Romina; Pellón Maisón, Magalí; Croce, María Virginia; Aldaz, C. Marcelo; Abba, Martín Carlos
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Rhomboid domain containing 2 (RHBDD2) was previously observed overexpressed and amplified in breast cancer samples. In order to identify biological pathways modulated by RHBDD2, gene expression profiles of RHBDD2 silenced breast cancer cells were analyzed using whole genome human microarray. Among the statistically significant overrepresented biological processes, we found protein metabolism—with the associated ontological terms folding , ubiquitination, and proteosomal degradation—cell death, cell cycle, and oxidative phosphorylation. In addition, we performed an in silico analysis searching for RHBDD2 co-expressed genes in several human tissues. Interestingly, the functional analysis of these genes showed similar results to those obtained with the microarray data, with negative regulation of protein metabolism and oxidative phosphorylation as the most enriched gene ontology terms. These data led us to hypothesize that RHBDD2 might be involved in endoplasmic reticulum (ER) stress response. Thus, we specifically analyzed the unfolding protein response (UPR) of the ER stress process. We used a lentivirus-based approach for stable silencing of RHBDD2 mRNA in the T47D breast cancer cell line, and we examined the transcriptional consequences on UPR genes as well as the phenotypic effects on migration and proliferation processes. By employing dithiothreitol as an UPR inducer, we observed that cells with silenced RHBDD2 showed increased expression of ATF6, IRE1, PERK, CRT, BiP, ATF4, and CHOP (p < 0.01). We also observed that RHBDD2 silencing inhibited colony formation and decreased cell migration. Based on these studies, we hypothesize that RHBDD2 overexpression in breast cancer could represent an adaptive phenotype to the stressful tumor microenvironment by modulating the ER stress response.
Facultad de Ciencias Médicas
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
Instituto de Investigaciones Bioquímicas de La Plata
Materia
Medicina
Bioquímica
RHBDD2
Breast cancer
ER stress
UPR
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/127224

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network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein responseLacunza, EzequielRabassa, Martín EnriqueCanzoneri, RominaPellón Maisón, MagalíCroce, María VirginiaAldaz, C. MarceloAbba, Martín CarlosMedicinaBioquímicaRHBDD2Breast cancerER stressUPRRhomboid domain containing 2 (RHBDD2) was previously observed overexpressed and amplified in breast cancer samples. In order to identify biological pathways modulated by RHBDD2, gene expression profiles of RHBDD2 silenced breast cancer cells were analyzed using whole genome human microarray. Among the statistically significant overrepresented biological processes, we found protein metabolism—with the associated ontological terms folding , ubiquitination, and proteosomal degradation—cell death, cell cycle, and oxidative phosphorylation. In addition, we performed an in silico analysis searching for RHBDD2 co-expressed genes in several human tissues. Interestingly, the functional analysis of these genes showed similar results to those obtained with the microarray data, with negative regulation of protein metabolism and oxidative phosphorylation as the most enriched gene ontology terms. These data led us to hypothesize that RHBDD2 might be involved in endoplasmic reticulum (ER) stress response. Thus, we specifically analyzed the unfolding protein response (UPR) of the ER stress process. We used a lentivirus-based approach for stable silencing of RHBDD2 mRNA in the T47D breast cancer cell line, and we examined the transcriptional consequences on UPR genes as well as the phenotypic effects on migration and proliferation processes. By employing dithiothreitol as an UPR inducer, we observed that cells with silenced RHBDD2 showed increased expression of ATF6, IRE1, PERK, CRT, BiP, ATF4, and CHOP (p < 0.01). We also observed that RHBDD2 silencing inhibited colony formation and decreased cell migration. Based on these studies, we hypothesize that RHBDD2 overexpression in breast cancer could represent an adaptive phenotype to the stressful tumor microenvironment by modulating the ER stress response.Facultad de Ciencias MédicasCentro de Investigaciones Inmunológicas Básicas y AplicadasInstituto de Investigaciones Bioquímicas de La Plata2014-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf379-388http://sedici.unlp.edu.ar/handle/10915/127224enginfo:eu-repo/semantics/altIdentifier/issn/1466-1268info:eu-repo/semantics/altIdentifier/issn/1355-8145info:eu-repo/semantics/altIdentifier/pmid/24078384info:eu-repo/semantics/altIdentifier/doi/10.1007/s12192-013-0466-3info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:30:42Zoai:sedici.unlp.edu.ar:10915/127224Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:30:43.045SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein response
title Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein response
spellingShingle Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein response
Lacunza, Ezequiel
Medicina
Bioquímica
RHBDD2
Breast cancer
ER stress
UPR
title_short Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein response
title_full Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein response
title_fullStr Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein response
title_full_unstemmed Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein response
title_sort Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein response
dc.creator.none.fl_str_mv Lacunza, Ezequiel
Rabassa, Martín Enrique
Canzoneri, Romina
Pellón Maisón, Magalí
Croce, María Virginia
Aldaz, C. Marcelo
Abba, Martín Carlos
author Lacunza, Ezequiel
author_facet Lacunza, Ezequiel
Rabassa, Martín Enrique
Canzoneri, Romina
Pellón Maisón, Magalí
Croce, María Virginia
Aldaz, C. Marcelo
Abba, Martín Carlos
author_role author
author2 Rabassa, Martín Enrique
Canzoneri, Romina
Pellón Maisón, Magalí
Croce, María Virginia
Aldaz, C. Marcelo
Abba, Martín Carlos
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Medicina
Bioquímica
RHBDD2
Breast cancer
ER stress
UPR
topic Medicina
Bioquímica
RHBDD2
Breast cancer
ER stress
UPR
dc.description.none.fl_txt_mv Rhomboid domain containing 2 (RHBDD2) was previously observed overexpressed and amplified in breast cancer samples. In order to identify biological pathways modulated by RHBDD2, gene expression profiles of RHBDD2 silenced breast cancer cells were analyzed using whole genome human microarray. Among the statistically significant overrepresented biological processes, we found protein metabolism—with the associated ontological terms folding , ubiquitination, and proteosomal degradation—cell death, cell cycle, and oxidative phosphorylation. In addition, we performed an in silico analysis searching for RHBDD2 co-expressed genes in several human tissues. Interestingly, the functional analysis of these genes showed similar results to those obtained with the microarray data, with negative regulation of protein metabolism and oxidative phosphorylation as the most enriched gene ontology terms. These data led us to hypothesize that RHBDD2 might be involved in endoplasmic reticulum (ER) stress response. Thus, we specifically analyzed the unfolding protein response (UPR) of the ER stress process. We used a lentivirus-based approach for stable silencing of RHBDD2 mRNA in the T47D breast cancer cell line, and we examined the transcriptional consequences on UPR genes as well as the phenotypic effects on migration and proliferation processes. By employing dithiothreitol as an UPR inducer, we observed that cells with silenced RHBDD2 showed increased expression of ATF6, IRE1, PERK, CRT, BiP, ATF4, and CHOP (p < 0.01). We also observed that RHBDD2 silencing inhibited colony formation and decreased cell migration. Based on these studies, we hypothesize that RHBDD2 overexpression in breast cancer could represent an adaptive phenotype to the stressful tumor microenvironment by modulating the ER stress response.
Facultad de Ciencias Médicas
Centro de Investigaciones Inmunológicas Básicas y Aplicadas
Instituto de Investigaciones Bioquímicas de La Plata
description Rhomboid domain containing 2 (RHBDD2) was previously observed overexpressed and amplified in breast cancer samples. In order to identify biological pathways modulated by RHBDD2, gene expression profiles of RHBDD2 silenced breast cancer cells were analyzed using whole genome human microarray. Among the statistically significant overrepresented biological processes, we found protein metabolism—with the associated ontological terms folding , ubiquitination, and proteosomal degradation—cell death, cell cycle, and oxidative phosphorylation. In addition, we performed an in silico analysis searching for RHBDD2 co-expressed genes in several human tissues. Interestingly, the functional analysis of these genes showed similar results to those obtained with the microarray data, with negative regulation of protein metabolism and oxidative phosphorylation as the most enriched gene ontology terms. These data led us to hypothesize that RHBDD2 might be involved in endoplasmic reticulum (ER) stress response. Thus, we specifically analyzed the unfolding protein response (UPR) of the ER stress process. We used a lentivirus-based approach for stable silencing of RHBDD2 mRNA in the T47D breast cancer cell line, and we examined the transcriptional consequences on UPR genes as well as the phenotypic effects on migration and proliferation processes. By employing dithiothreitol as an UPR inducer, we observed that cells with silenced RHBDD2 showed increased expression of ATF6, IRE1, PERK, CRT, BiP, ATF4, and CHOP (p < 0.01). We also observed that RHBDD2 silencing inhibited colony formation and decreased cell migration. Based on these studies, we hypothesize that RHBDD2 overexpression in breast cancer could represent an adaptive phenotype to the stressful tumor microenvironment by modulating the ER stress response.
publishDate 2014
dc.date.none.fl_str_mv 2014-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/127224
url http://sedici.unlp.edu.ar/handle/10915/127224
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1466-1268
info:eu-repo/semantics/altIdentifier/issn/1355-8145
info:eu-repo/semantics/altIdentifier/pmid/24078384
info:eu-repo/semantics/altIdentifier/doi/10.1007/s12192-013-0466-3
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
379-388
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repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
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