Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model.

Epithelial-to-mesenchymal transition (EMT), the phenotypical change of cells from an epithelial to a mesenchymal type, is thought to be a key event in invasion and metastasis of adenocarcinomas. These changes involve loss of keratin expression as well as loss of cell polarity and adhesion. We here a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Katharina König, Lydia Meder, Cornelia Kröger, Linda Diehl, Alexandra Florin, Ursula Rommerscheidt-Fuss, Philip Kahl, Eva Wardelmann, Thomas M Magin, Reinhard Buettner, Lukas C Heukamp
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/80708e14f49540c2bf49cca0a3aa43ab
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:80708e14f49540c2bf49cca0a3aa43ab
record_format	dspace
spelling	oai:doaj.org-article:80708e14f49540c2bf49cca0a3aa43ab2021-11-18T07:54:00ZLoss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model.1932-620310.1371/journal.pone.0057996https://doaj.org/article/80708e14f49540c2bf49cca0a3aa43ab2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23536778/?tool=EBIhttps://doaj.org/toc/1932-6203Epithelial-to-mesenchymal transition (EMT), the phenotypical change of cells from an epithelial to a mesenchymal type, is thought to be a key event in invasion and metastasis of adenocarcinomas. These changes involve loss of keratin expression as well as loss of cell polarity and adhesion. We here aimed to determine whether the loss of keratin expression itself drives increased invasion and metastasis in adenocarcinomas and whether keratin loss leads to the phenotypic changes associated with EMT. Therefore, we employed a recently described murine model in which conditional deletion of the Keratin cluster II by Cre-recombinase leads to the loss of the entire keratinmultiprotein family. These mice were crossed into a newly generated Cre-recombinase inducible KRAS-driven murine lung cancer model to examine the effect of keratin loss on morphology, invasion and metastasis as well as expression of EMT related genes in the resulting tumors. We here clearly show that loss of a functional keratin cytoskeleton did not significantly alter tumor morphology or biology in terms of invasion, metastasis, proliferation or tumor burden and did not lead to induction of EMT. Further, tumor cells did not induce synchronously expression of vimentin, which is often seen in EMT, to compensate for keratin loss. In summary, our data suggest that changes in cell shape and migration that underlie EMT are dependent on changes in signaling pathways that cause secondary changes in keratin expression and organization. Thus, we conclude that loss of the keratin cytoskeleton per se is not sufficient to causally drive EMT in this tumor model.Katharina KönigLydia MederCornelia KrögerLinda DiehlAlexandra FlorinUrsula Rommerscheidt-FussPhilip KahlEva WardelmannThomas M MaginReinhard BuettnerLukas C HeukampPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e57996 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katharina König Lydia Meder Cornelia Kröger Linda Diehl Alexandra Florin Ursula Rommerscheidt-Fuss Philip Kahl Eva Wardelmann Thomas M Magin Reinhard Buettner Lukas C Heukamp Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model.
description	Epithelial-to-mesenchymal transition (EMT), the phenotypical change of cells from an epithelial to a mesenchymal type, is thought to be a key event in invasion and metastasis of adenocarcinomas. These changes involve loss of keratin expression as well as loss of cell polarity and adhesion. We here aimed to determine whether the loss of keratin expression itself drives increased invasion and metastasis in adenocarcinomas and whether keratin loss leads to the phenotypic changes associated with EMT. Therefore, we employed a recently described murine model in which conditional deletion of the Keratin cluster II by Cre-recombinase leads to the loss of the entire keratinmultiprotein family. These mice were crossed into a newly generated Cre-recombinase inducible KRAS-driven murine lung cancer model to examine the effect of keratin loss on morphology, invasion and metastasis as well as expression of EMT related genes in the resulting tumors. We here clearly show that loss of a functional keratin cytoskeleton did not significantly alter tumor morphology or biology in terms of invasion, metastasis, proliferation or tumor burden and did not lead to induction of EMT. Further, tumor cells did not induce synchronously expression of vimentin, which is often seen in EMT, to compensate for keratin loss. In summary, our data suggest that changes in cell shape and migration that underlie EMT are dependent on changes in signaling pathways that cause secondary changes in keratin expression and organization. Thus, we conclude that loss of the keratin cytoskeleton per se is not sufficient to causally drive EMT in this tumor model.
format	article
author	Katharina König Lydia Meder Cornelia Kröger Linda Diehl Alexandra Florin Ursula Rommerscheidt-Fuss Philip Kahl Eva Wardelmann Thomas M Magin Reinhard Buettner Lukas C Heukamp
author_facet	Katharina König Lydia Meder Cornelia Kröger Linda Diehl Alexandra Florin Ursula Rommerscheidt-Fuss Philip Kahl Eva Wardelmann Thomas M Magin Reinhard Buettner Lukas C Heukamp
author_sort	Katharina König
title	Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model.
title_short	Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model.
title_full	Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model.
title_fullStr	Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model.
title_full_unstemmed	Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model.
title_sort	loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel kras driven sporadic lung cancer mouse model.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/80708e14f49540c2bf49cca0a3aa43ab
work_keys_str_mv	AT katharinakonig lossofthekeratincytoskeletonisnotsufficienttoinduceepithelialmesenchymaltransitioninanovelkrasdrivensporadiclungcancermousemodel AT lydiameder lossofthekeratincytoskeletonisnotsufficienttoinduceepithelialmesenchymaltransitioninanovelkrasdrivensporadiclungcancermousemodel AT corneliakroger lossofthekeratincytoskeletonisnotsufficienttoinduceepithelialmesenchymaltransitioninanovelkrasdrivensporadiclungcancermousemodel AT lindadiehl lossofthekeratincytoskeletonisnotsufficienttoinduceepithelialmesenchymaltransitioninanovelkrasdrivensporadiclungcancermousemodel AT alexandraflorin lossofthekeratincytoskeletonisnotsufficienttoinduceepithelialmesenchymaltransitioninanovelkrasdrivensporadiclungcancermousemodel AT ursularommerscheidtfuss lossofthekeratincytoskeletonisnotsufficienttoinduceepithelialmesenchymaltransitioninanovelkrasdrivensporadiclungcancermousemodel AT philipkahl lossofthekeratincytoskeletonisnotsufficienttoinduceepithelialmesenchymaltransitioninanovelkrasdrivensporadiclungcancermousemodel AT evawardelmann lossofthekeratincytoskeletonisnotsufficienttoinduceepithelialmesenchymaltransitioninanovelkrasdrivensporadiclungcancermousemodel AT thomasmmagin lossofthekeratincytoskeletonisnotsufficienttoinduceepithelialmesenchymaltransitioninanovelkrasdrivensporadiclungcancermousemodel AT reinhardbuettner lossofthekeratincytoskeletonisnotsufficienttoinduceepithelialmesenchymaltransitioninanovelkrasdrivensporadiclungcancermousemodel AT lukascheukamp lossofthekeratincytoskeletonisnotsufficienttoinduceepithelialmesenchymaltransitioninanovelkrasdrivensporadiclungcancermousemodel
_version_	1718422787851288576

Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model.

Ejemplares similares