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

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 t...

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Detalles Bibliográficos
Autores principales: Lacunza, Ezequiel, Rabassa, Martín Enrique, Canzoneri, Romina, Pellón Maisón, Magalí, Croce, María Virginia, Aldaz, C. Marcelo, Abba, Martín Carlos
Formato: Articulo
Lenguaje:Inglés
Publicado: 2014
Materias:
Medicina
Bioquímica
RHBDD2
Breast cancer
ER stress
UPR
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/127224
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-127224
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Medicina
Bioquímica
RHBDD2
Breast cancer
ER stress
UPR
spellingShingle Medicina
Bioquímica
RHBDD2
Breast cancer
ER stress
UPR
Lacunza, Ezequiel
Rabassa, Martín Enrique
Canzoneri, Romina
Pellón Maisón, Magalí
Croce, María Virginia
Aldaz, C. Marcelo
Abba, Martín Carlos
Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein response
topic_facet Medicina
Bioquímica
RHBDD2
Breast cancer
ER stress
UPR
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.
format Articulo
Articulo
author Lacunza, Ezequiel
Rabassa, Martín Enrique
Canzoneri, Romina
Pellón Maisón, Magalí
Croce, María Virginia
Aldaz, C. Marcelo
Abba, Martín Carlos
author_facet Lacunza, Ezequiel
Rabassa, Martín Enrique
Canzoneri, Romina
Pellón Maisón, Magalí
Croce, María Virginia
Aldaz, C. Marcelo
Abba, Martín Carlos
author_sort Lacunza, Ezequiel
title Identification of signaling pathways modulated by RHBDD2 in breast cancer cells: a link to the unfolded protein response
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
publishDate 2014
url http://sedici.unlp.edu.ar/handle/10915/127224
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