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Krüppel-Like Factor 6 Is Required for Oxidative and Oncogene-Induced Cellular Senescence

Krüppel-like factor 6 (KLF6) is a transcription factor involved in the regulation of several cellular processes. Regarding its role in tumorigenesis, KLF6 is considered a tumor suppressor. Numerous reports demonstrate its frequent genomic loss or down-regulation, implying a functional inactivation i...

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Autores principales: Sabatino, Maria Eugenia, Castellaro, Andrés, Racca, Ana C., Carbajosa González, Sofía, Pansa, Maria Florencia, Soria, Gastón, Bocco, Jose Luis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882731/
https://www.ncbi.nlm.nih.gov/pubmed/31824948
http://dx.doi.org/10.3389/fcell.2019.00297
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author Sabatino, Maria Eugenia
Castellaro, Andrés
Racca, Ana C.
Carbajosa González, Sofía
Pansa, Maria Florencia
Soria, Gastón
Bocco, Jose Luis
author_facet Sabatino, Maria Eugenia
Castellaro, Andrés
Racca, Ana C.
Carbajosa González, Sofía
Pansa, Maria Florencia
Soria, Gastón
Bocco, Jose Luis
author_sort Sabatino, Maria Eugenia
collection PubMed
description Krüppel-like factor 6 (KLF6) is a transcription factor involved in the regulation of several cellular processes. Regarding its role in tumorigenesis, KLF6 is considered a tumor suppressor. Numerous reports demonstrate its frequent genomic loss or down-regulation, implying a functional inactivation in a broad range of human cancers. Previous work from our laboratory showed that the down-regulation of KLF6 expression in normal fibroblasts leads to cellular transformation, while its ectopic expression interferes with the oncogenic transformation triggered by activated Ras through a cell cycle arrest. We hypothesize that the growth suppressor activity of KLF6 may involve the induction of cellular senescence thereby helping to prevent the proliferation of cells at risk of neoplastic transformation. Here, we explored the association of KLF6 up-regulation in two different cellular senescence scenarios. We found that KLF6 silencing bypasses both oxidative and oncogene-induced senescence. In this context, KLF6 expression per se was capable to trigger cellular senescence in both normal and tumoral contexts. As such, the findings presented in this report provide insights into a potential mechanism by which KLF6 may play a suppressing role of uncontrolled or damaged cell proliferation.
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spelling pubmed-68827312019-12-10 Krüppel-Like Factor 6 Is Required for Oxidative and Oncogene-Induced Cellular Senescence Sabatino, Maria Eugenia Castellaro, Andrés Racca, Ana C. Carbajosa González, Sofía Pansa, Maria Florencia Soria, Gastón Bocco, Jose Luis Front Cell Dev Biol Cell and Developmental Biology Krüppel-like factor 6 (KLF6) is a transcription factor involved in the regulation of several cellular processes. Regarding its role in tumorigenesis, KLF6 is considered a tumor suppressor. Numerous reports demonstrate its frequent genomic loss or down-regulation, implying a functional inactivation in a broad range of human cancers. Previous work from our laboratory showed that the down-regulation of KLF6 expression in normal fibroblasts leads to cellular transformation, while its ectopic expression interferes with the oncogenic transformation triggered by activated Ras through a cell cycle arrest. We hypothesize that the growth suppressor activity of KLF6 may involve the induction of cellular senescence thereby helping to prevent the proliferation of cells at risk of neoplastic transformation. Here, we explored the association of KLF6 up-regulation in two different cellular senescence scenarios. We found that KLF6 silencing bypasses both oxidative and oncogene-induced senescence. In this context, KLF6 expression per se was capable to trigger cellular senescence in both normal and tumoral contexts. As such, the findings presented in this report provide insights into a potential mechanism by which KLF6 may play a suppressing role of uncontrolled or damaged cell proliferation. Frontiers Media S.A. 2019-11-22 /pmc/articles/PMC6882731/ /pubmed/31824948 http://dx.doi.org/10.3389/fcell.2019.00297 Text en Copyright © 2019 Sabatino, Castellaro, Racca, Carbajosa González, Pansa, Soria and Bocco. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Sabatino, Maria Eugenia
Castellaro, Andrés
Racca, Ana C.
Carbajosa González, Sofía
Pansa, Maria Florencia
Soria, Gastón
Bocco, Jose Luis
Krüppel-Like Factor 6 Is Required for Oxidative and Oncogene-Induced Cellular Senescence
title Krüppel-Like Factor 6 Is Required for Oxidative and Oncogene-Induced Cellular Senescence
title_full Krüppel-Like Factor 6 Is Required for Oxidative and Oncogene-Induced Cellular Senescence
title_fullStr Krüppel-Like Factor 6 Is Required for Oxidative and Oncogene-Induced Cellular Senescence
title_full_unstemmed Krüppel-Like Factor 6 Is Required for Oxidative and Oncogene-Induced Cellular Senescence
title_short Krüppel-Like Factor 6 Is Required for Oxidative and Oncogene-Induced Cellular Senescence
title_sort krüppel-like factor 6 is required for oxidative and oncogene-induced cellular senescence
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6882731/
https://www.ncbi.nlm.nih.gov/pubmed/31824948
http://dx.doi.org/10.3389/fcell.2019.00297
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