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A Novel Role for the Tumor Suppressor Gene ITF2 in Tumorigenesis and Chemotherapy Response

Despite often leading to platinum resistance, platinum-based chemotherapy continues to be the standard treatment for many epithelial tumors. In this study we analyzed and validated the cytogenetic alterations that arise after treatment in four lung and ovarian paired cisplatin-sensitive/resistant ce...

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Autores principales: Pernía, Olga, Sastre-Perona, Ana, Rodriguez-Antolín, Carlos, García-Guede, Alvaro, Palomares-Bralo, María, Rosas, Rocío, Sanchez-Cabrero, Darío, Cruz, Patricia, Rodriguez, Carmen, Diestro, MDolores, Martín-Arenas, Rubén, Pulido, Verónica, Santisteban, Pilar, de Castro, Javier, Vera, Olga, Ibáñez de Cáceres, Inmaculada
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226299/
https://www.ncbi.nlm.nih.gov/pubmed/32224864
http://dx.doi.org/10.3390/cancers12040786
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author Pernía, Olga
Sastre-Perona, Ana
Rodriguez-Antolín, Carlos
García-Guede, Alvaro
Palomares-Bralo, María
Rosas, Rocío
Sanchez-Cabrero, Darío
Cruz, Patricia
Rodriguez, Carmen
Diestro, MDolores
Martín-Arenas, Rubén
Pulido, Verónica
Santisteban, Pilar
de Castro, Javier
Vera, Olga
Ibáñez de Cáceres, Inmaculada
author_facet Pernía, Olga
Sastre-Perona, Ana
Rodriguez-Antolín, Carlos
García-Guede, Alvaro
Palomares-Bralo, María
Rosas, Rocío
Sanchez-Cabrero, Darío
Cruz, Patricia
Rodriguez, Carmen
Diestro, MDolores
Martín-Arenas, Rubén
Pulido, Verónica
Santisteban, Pilar
de Castro, Javier
Vera, Olga
Ibáñez de Cáceres, Inmaculada
author_sort Pernía, Olga
collection PubMed
description Despite often leading to platinum resistance, platinum-based chemotherapy continues to be the standard treatment for many epithelial tumors. In this study we analyzed and validated the cytogenetic alterations that arise after treatment in four lung and ovarian paired cisplatin-sensitive/resistant cell lines by 1-million microarray-based comparative genomic hybridization (array-CGH) and qRT-PCR methodologies. RNA-sequencing, functional transfection assays, and gene-pathway activity analysis were used to identify genes with a potential role in the development of this malignancy. The results were further explored in 55 lung and ovarian primary tumors and control samples, and in two extensive in silico databases. Long-term cell exposure to platinum induces the frequent deletion of ITF2 gene. Its expression re-sensitized tumor cells to platinum and recovered the levels of Wnt/β-catenin transcriptional activity. ITF2 expression was also frequently downregulated in epithelial tumors, predicting a worse overall survival. We also identified an inverse correlation between ITF2 and HOXD9 expression, revealing that Non-small cell lung cancer (NSCLC) patients with lower expression of HOXD9 had a better overall survival rate. We defined the implication of ITF2 as a molecular mechanism behind the development of cisplatin resistance probably through the activation of the Wnt-signaling pathway. This data highlights the possible role of ITF2 and HOXD9 as novel therapeutic targets for platinum resistant tumors.
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spelling pubmed-72262992020-05-18 A Novel Role for the Tumor Suppressor Gene ITF2 in Tumorigenesis and Chemotherapy Response Pernía, Olga Sastre-Perona, Ana Rodriguez-Antolín, Carlos García-Guede, Alvaro Palomares-Bralo, María Rosas, Rocío Sanchez-Cabrero, Darío Cruz, Patricia Rodriguez, Carmen Diestro, MDolores Martín-Arenas, Rubén Pulido, Verónica Santisteban, Pilar de Castro, Javier Vera, Olga Ibáñez de Cáceres, Inmaculada Cancers (Basel) Article Despite often leading to platinum resistance, platinum-based chemotherapy continues to be the standard treatment for many epithelial tumors. In this study we analyzed and validated the cytogenetic alterations that arise after treatment in four lung and ovarian paired cisplatin-sensitive/resistant cell lines by 1-million microarray-based comparative genomic hybridization (array-CGH) and qRT-PCR methodologies. RNA-sequencing, functional transfection assays, and gene-pathway activity analysis were used to identify genes with a potential role in the development of this malignancy. The results were further explored in 55 lung and ovarian primary tumors and control samples, and in two extensive in silico databases. Long-term cell exposure to platinum induces the frequent deletion of ITF2 gene. Its expression re-sensitized tumor cells to platinum and recovered the levels of Wnt/β-catenin transcriptional activity. ITF2 expression was also frequently downregulated in epithelial tumors, predicting a worse overall survival. We also identified an inverse correlation between ITF2 and HOXD9 expression, revealing that Non-small cell lung cancer (NSCLC) patients with lower expression of HOXD9 had a better overall survival rate. We defined the implication of ITF2 as a molecular mechanism behind the development of cisplatin resistance probably through the activation of the Wnt-signaling pathway. This data highlights the possible role of ITF2 and HOXD9 as novel therapeutic targets for platinum resistant tumors. MDPI 2020-03-26 /pmc/articles/PMC7226299/ /pubmed/32224864 http://dx.doi.org/10.3390/cancers12040786 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pernía, Olga
Sastre-Perona, Ana
Rodriguez-Antolín, Carlos
García-Guede, Alvaro
Palomares-Bralo, María
Rosas, Rocío
Sanchez-Cabrero, Darío
Cruz, Patricia
Rodriguez, Carmen
Diestro, MDolores
Martín-Arenas, Rubén
Pulido, Verónica
Santisteban, Pilar
de Castro, Javier
Vera, Olga
Ibáñez de Cáceres, Inmaculada
A Novel Role for the Tumor Suppressor Gene ITF2 in Tumorigenesis and Chemotherapy Response
title A Novel Role for the Tumor Suppressor Gene ITF2 in Tumorigenesis and Chemotherapy Response
title_full A Novel Role for the Tumor Suppressor Gene ITF2 in Tumorigenesis and Chemotherapy Response
title_fullStr A Novel Role for the Tumor Suppressor Gene ITF2 in Tumorigenesis and Chemotherapy Response
title_full_unstemmed A Novel Role for the Tumor Suppressor Gene ITF2 in Tumorigenesis and Chemotherapy Response
title_short A Novel Role for the Tumor Suppressor Gene ITF2 in Tumorigenesis and Chemotherapy Response
title_sort novel role for the tumor suppressor gene itf2 in tumorigenesis and chemotherapy response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226299/
https://www.ncbi.nlm.nih.gov/pubmed/32224864
http://dx.doi.org/10.3390/cancers12040786
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