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
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/127224
Ver los metadatos del registro completo
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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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