p38α Negatively Regulates Survival and Malignant Selection of Transformed Bronchioalveolar Stem Cells

Lung cancer is the cause of most cancer-related deaths in the Western world. Non-small cell lung cancer accounts for almost 80% of all lung cancers, and 50% of this type are adenocarcinomas. The cellular and molecular origin of this type of lung cancer remains elusive and the mechanisms are poorly k...

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Autores principales: Voisset, Edwige, Oeztuerk-Winder, Feride, Ruiz, Edgar-Josue, Ventura, Juan-Jose
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827089/
https://www.ncbi.nlm.nih.gov/pubmed/24265727
http://dx.doi.org/10.1371/journal.pone.0078911
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author Voisset, Edwige
Oeztuerk-Winder, Feride
Ruiz, Edgar-Josue
Ventura, Juan-Jose
author_facet Voisset, Edwige
Oeztuerk-Winder, Feride
Ruiz, Edgar-Josue
Ventura, Juan-Jose
author_sort Voisset, Edwige
collection PubMed
description Lung cancer is the cause of most cancer-related deaths in the Western world. Non-small cell lung cancer accounts for almost 80% of all lung cancers, and 50% of this type are adenocarcinomas. The cellular and molecular origin of this type of lung cancer remains elusive and the mechanisms are poorly known. It is known that K-Ras mutations appear in 25–30% of lung adenocarcinomas and it is the best known single mutation that can be related to lung cancers. Recently, it has been suggested that a putative population of mouse bronchioalveolar stem cells could be considered as the cell of origin of adenocarcinomas. These cells are expanded in the early stages of lung tumorigenesis. We have isolated a population of mouse bronchioalveolar stem cells and induced their transformation by oncogenic K-RasG12. Different approaches have shown that an intracellular network linking the p38α MAPK and the PI3K-Pdk1 pathways is involved in regulating the survival and malignant progression of the transformed cells. Absence of p38α catalytic activity leads to further Pdk1 activation (independent of Akt and Erk activity), enhancing the survival and proliferation of the more malignant lung cancer cells. This specifically selects high Sca-1/Sox9 cells that harbour a stronger colonizing potential, as they maintain their capacity to produce secondary tumors after serial transplantations.
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spelling pubmed-38270892013-11-21 p38α Negatively Regulates Survival and Malignant Selection of Transformed Bronchioalveolar Stem Cells Voisset, Edwige Oeztuerk-Winder, Feride Ruiz, Edgar-Josue Ventura, Juan-Jose PLoS One Research Article Lung cancer is the cause of most cancer-related deaths in the Western world. Non-small cell lung cancer accounts for almost 80% of all lung cancers, and 50% of this type are adenocarcinomas. The cellular and molecular origin of this type of lung cancer remains elusive and the mechanisms are poorly known. It is known that K-Ras mutations appear in 25–30% of lung adenocarcinomas and it is the best known single mutation that can be related to lung cancers. Recently, it has been suggested that a putative population of mouse bronchioalveolar stem cells could be considered as the cell of origin of adenocarcinomas. These cells are expanded in the early stages of lung tumorigenesis. We have isolated a population of mouse bronchioalveolar stem cells and induced their transformation by oncogenic K-RasG12. Different approaches have shown that an intracellular network linking the p38α MAPK and the PI3K-Pdk1 pathways is involved in regulating the survival and malignant progression of the transformed cells. Absence of p38α catalytic activity leads to further Pdk1 activation (independent of Akt and Erk activity), enhancing the survival and proliferation of the more malignant lung cancer cells. This specifically selects high Sca-1/Sox9 cells that harbour a stronger colonizing potential, as they maintain their capacity to produce secondary tumors after serial transplantations. Public Library of Science 2013-11-12 /pmc/articles/PMC3827089/ /pubmed/24265727 http://dx.doi.org/10.1371/journal.pone.0078911 Text en © 2013 Voisset et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Voisset, Edwige
Oeztuerk-Winder, Feride
Ruiz, Edgar-Josue
Ventura, Juan-Jose
p38α Negatively Regulates Survival and Malignant Selection of Transformed Bronchioalveolar Stem Cells
title p38α Negatively Regulates Survival and Malignant Selection of Transformed Bronchioalveolar Stem Cells
title_full p38α Negatively Regulates Survival and Malignant Selection of Transformed Bronchioalveolar Stem Cells
title_fullStr p38α Negatively Regulates Survival and Malignant Selection of Transformed Bronchioalveolar Stem Cells
title_full_unstemmed p38α Negatively Regulates Survival and Malignant Selection of Transformed Bronchioalveolar Stem Cells
title_short p38α Negatively Regulates Survival and Malignant Selection of Transformed Bronchioalveolar Stem Cells
title_sort p38α negatively regulates survival and malignant selection of transformed bronchioalveolar stem cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827089/
https://www.ncbi.nlm.nih.gov/pubmed/24265727
http://dx.doi.org/10.1371/journal.pone.0078911
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