Alternative splicing variant of RHBDD2 is associated with cell stress response and breast cancer progression

RHBDD2 is an intramembrane pseudoprotease member of the Rhomboid superfamily. Our previous studies in breast and colorectal cancer indicate an association between RHBDD2 overexpression and advanced tumor stages. Two alternative transcriptional variants have been described for RHBDD2, which would be...

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Autores principales: Canzoneri, Romina, Rabassa, Martín Enrique, Gurruchaga, Agustina, Ferretti, Valeria Alejandra, Palma, Sabina, Isla Larrain, Marina Teresita, Croce, María Virginia, Lacunza, Ezequiel, Abba, Martín Carlos
Formato: Articulo
Lenguaje:Inglés
Publicado: 2018
Materias:
Medicina
RHBDD2
breast cancer
protein isoform
subcellular localization
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/131464
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-131464
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Medicina
RHBDD2
breast cancer
protein isoform
subcellular localization
spellingShingle Medicina
RHBDD2
breast cancer
protein isoform
subcellular localization
Canzoneri, Romina
Rabassa, Martín Enrique
Gurruchaga, Agustina
Ferretti, Valeria Alejandra
Palma, Sabina
Isla Larrain, Marina Teresita
Croce, María Virginia
Lacunza, Ezequiel
Abba, Martín Carlos
Alternative splicing variant of RHBDD2 is associated with cell stress response and breast cancer progression
topic_facet Medicina
RHBDD2
breast cancer
protein isoform
subcellular localization
description RHBDD2 is an intramembrane pseudoprotease member of the Rhomboid superfamily. Our previous studies in breast and colorectal cancer indicate an association between RHBDD2 overexpression and advanced tumor stages. Two alternative transcriptional variants have been described for RHBDD2, which would be encoding for different RHBDD2 protein isoforms. The expression of these RHBDD2 variants/isoforms and its association with breast cancer was the focus of this study. First, expression of RHBDD2 splicing variants was evaluated in normal and breast tumor samples. RHBDD2 variant 2 overexpression was detected in tumors in respect to normal breast tissues at the mRNA and protein levels (P<0.05). Moreover, RHBDD2 variant 2 expression was associated with poor prognostic factors such as basal‑like intrinsic subtype (P<0.05), high proliferation (P<0.01) and long‑term risk‑of‑recurrence (P<0.01) scores. Second, the expression of both variants was evaluated under nutritional‑deprived conditions in breast cancer cell lines. Results demonstrated that RHBDD2 splicing was switched from mRNA variant 1 to variant 2 in association with a significant increment of protein isoform B in response to glucose starvation treatment. Therefore, we propose that the switch from the RHBDD2 variant 1, expressed in normal epithelial cells, to variant 2 occurs as an adaptive phenotype to bypass the stressful tumor microenvironment and promote tumor progression. Finally, the RHBDD2 subcellular localization was corroborated at the Golgi apparatus and their associated v‑SNARE transport vesicles, suggesting a putative new role for RHBDD2 in the protein trafficking of human breast cancer cells.
format Articulo
Articulo
author Canzoneri, Romina
Rabassa, Martín Enrique
Gurruchaga, Agustina
Ferretti, Valeria Alejandra
Palma, Sabina
Isla Larrain, Marina Teresita
Croce, María Virginia
Lacunza, Ezequiel
Abba, Martín Carlos
author_facet Canzoneri, Romina
Rabassa, Martín Enrique
Gurruchaga, Agustina
Ferretti, Valeria Alejandra
Palma, Sabina
Isla Larrain, Marina Teresita
Croce, María Virginia
Lacunza, Ezequiel
Abba, Martín Carlos
author_sort Canzoneri, Romina
title Alternative splicing variant of RHBDD2 is associated with cell stress response and breast cancer progression
title_short Alternative splicing variant of RHBDD2 is associated with cell stress response and breast cancer progression
title_full Alternative splicing variant of RHBDD2 is associated with cell stress response and breast cancer progression
title_fullStr Alternative splicing variant of RHBDD2 is associated with cell stress response and breast cancer progression
title_full_unstemmed Alternative splicing variant of RHBDD2 is associated with cell stress response and breast cancer progression
title_sort alternative splicing variant of rhbdd2 is associated with cell stress response and breast cancer progression
publishDate 2018
url http://sedici.unlp.edu.ar/handle/10915/131464
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