Lkb1 loss promotes tumor progression of BRAF(V600E)-induced lung adenomas.

Aberrant activation of MAP kinase signaling pathway and loss of tumor suppressor LKB1 have been implicated in lung cancer development and progression. Although oncogenic KRAS mutations are frequent, BRAF mutations (BRAF(V600E)) are found in 3% of human non-small cell lung cancers. Contrary to KRAS m...

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Autores principales:	Elena González-Sánchez, Juan Martín-Caballero, Juana María Flores, Javier Hernández-Losa, Ma Ángeles Montero, Javier Cortés, Roso Mares, Mariano Barbacid, Juan A Recio
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9678441d61b544159212b4cfb22eb5a3
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spelling	oai:doaj.org-article:9678441d61b544159212b4cfb22eb5a32021-11-18T07:40:08ZLkb1 loss promotes tumor progression of BRAF(V600E)-induced lung adenomas.1932-620310.1371/journal.pone.0066933https://doaj.org/article/9678441d61b544159212b4cfb22eb5a32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23825589/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Aberrant activation of MAP kinase signaling pathway and loss of tumor suppressor LKB1 have been implicated in lung cancer development and progression. Although oncogenic KRAS mutations are frequent, BRAF mutations (BRAF(V600E)) are found in 3% of human non-small cell lung cancers. Contrary to KRAS mutant tumors, BRAF(V600E)-induced tumors are benign adenomas that fail to progess. Interestingly, loss of tumor supressor LKB1 coexists with KRAS oncogenic mutations and synergizes in tumor formation and progression, however, its cooperation with BRAF(V600E) oncogene is unknown. Our results describe a lung cell population in neonates mice where expression of BRAF(V600E) leads to lung adenoma development. Importantly, expression of BRAF(V600E) concomitant with the loss of only a single-copy of Lkb1, overcomes senencence-like features of BRAF(V600E)-mutant adenomas leading malignization to carcinomas. These results posit LKB1 haploinsufficiency as a risk factor for tumor progression of BRAF(V600E) mutated lung adenomas in human cancer patients.Elena González-SánchezJuan Martín-CaballeroJuana María FloresJavier Hernández-LosaMa Ángeles MonteroJavier CortésRoso MaresMariano BarbacidJuan A RecioPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e66933 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Elena González-Sánchez Juan Martín-Caballero Juana María Flores Javier Hernández-Losa Ma Ángeles Montero Javier Cortés Roso Mares Mariano Barbacid Juan A Recio Lkb1 loss promotes tumor progression of BRAF(V600E)-induced lung adenomas.
description	Aberrant activation of MAP kinase signaling pathway and loss of tumor suppressor LKB1 have been implicated in lung cancer development and progression. Although oncogenic KRAS mutations are frequent, BRAF mutations (BRAF(V600E)) are found in 3% of human non-small cell lung cancers. Contrary to KRAS mutant tumors, BRAF(V600E)-induced tumors are benign adenomas that fail to progess. Interestingly, loss of tumor supressor LKB1 coexists with KRAS oncogenic mutations and synergizes in tumor formation and progression, however, its cooperation with BRAF(V600E) oncogene is unknown. Our results describe a lung cell population in neonates mice where expression of BRAF(V600E) leads to lung adenoma development. Importantly, expression of BRAF(V600E) concomitant with the loss of only a single-copy of Lkb1, overcomes senencence-like features of BRAF(V600E)-mutant adenomas leading malignization to carcinomas. These results posit LKB1 haploinsufficiency as a risk factor for tumor progression of BRAF(V600E) mutated lung adenomas in human cancer patients.
format	article
author	Elena González-Sánchez Juan Martín-Caballero Juana María Flores Javier Hernández-Losa Ma Ángeles Montero Javier Cortés Roso Mares Mariano Barbacid Juan A Recio
author_facet	Elena González-Sánchez Juan Martín-Caballero Juana María Flores Javier Hernández-Losa Ma Ángeles Montero Javier Cortés Roso Mares Mariano Barbacid Juan A Recio
author_sort	Elena González-Sánchez
title	Lkb1 loss promotes tumor progression of BRAF(V600E)-induced lung adenomas.
title_short	Lkb1 loss promotes tumor progression of BRAF(V600E)-induced lung adenomas.
title_full	Lkb1 loss promotes tumor progression of BRAF(V600E)-induced lung adenomas.
title_fullStr	Lkb1 loss promotes tumor progression of BRAF(V600E)-induced lung adenomas.
title_full_unstemmed	Lkb1 loss promotes tumor progression of BRAF(V600E)-induced lung adenomas.
title_sort	lkb1 loss promotes tumor progression of braf(v600e)-induced lung adenomas.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9678441d61b544159212b4cfb22eb5a3
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Lkb1 loss promotes tumor progression of BRAF(V600E)-induced lung adenomas.

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