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

Standard

Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model. / König, Katharina; Meder, Lydia; Kröger, Cornelia; Diehl, Linda; Florin, Alexandra; Rommerscheidt-Fuss, Ursula; Kahl, Philip; Wardelmann, Eva; Magin, Thomas M; Buettner, Reinhard; Heukamp, Lukas C.

In: PLOS ONE, Vol. 8, No. 3, 2013, p. e57996.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

König, K, Meder, L, Kröger, C, Diehl, L, Florin, A, Rommerscheidt-Fuss, U, Kahl, P, Wardelmann, E, Magin, TM, Buettner, R & Heukamp, LC 2013, 'Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model', PLOS ONE, vol. 8, no. 3, pp. e57996. https://doi.org/10.1371/journal.pone.0057996

APA

König, K., Meder, L., Kröger, C., Diehl, L., Florin, A., Rommerscheidt-Fuss, U., Kahl, P., Wardelmann, E., Magin, T. M., Buettner, R., & Heukamp, L. C. (2013). Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model. PLOS ONE, 8(3), e57996. https://doi.org/10.1371/journal.pone.0057996

Vancouver

König K, Meder L, Kröger C, Diehl L, Florin A, Rommerscheidt-Fuss U et al. Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model. PLOS ONE. 2013;8(3):e57996. https://doi.org/10.1371/journal.pone.0057996

Bibtex

@article{a97877cebcad4eaa85c0f97144017a96,
title = "Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model",
abstract = "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.",
keywords = "Animals, Biomarkers, Carcinoma, Non-Small-Cell Lung, Cell Line, Disease Models, Animal, Epithelial-Mesenchymal Transition, Gene Expression Regulation, Neoplastic, Gene Order, Gene Targeting, Genes, ras, Humans, Keratins, Lung Neoplasms, Mice, Mice, Transgenic, Small Cell Lung Carcinoma",
author = "Katharina K{\"o}nig and Lydia Meder and Cornelia Kr{\"o}ger and Linda Diehl and Alexandra Florin and Ursula Rommerscheidt-Fuss and Philip Kahl and Eva Wardelmann and Magin, {Thomas M} and Reinhard Buettner and Heukamp, {Lukas C}",
year = "2013",
doi = "10.1371/journal.pone.0057996",
language = "English",
volume = "8",
pages = "e57996",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

RIS

TY - JOUR

T1 - Loss of the keratin cytoskeleton is not sufficient to induce epithelial mesenchymal transition in a novel KRAS driven sporadic lung cancer mouse model

AU - König, Katharina

AU - Meder, Lydia

AU - Kröger, Cornelia

AU - Diehl, Linda

AU - Florin, Alexandra

AU - Rommerscheidt-Fuss, Ursula

AU - Kahl, Philip

AU - Wardelmann, Eva

AU - Magin, Thomas M

AU - Buettner, Reinhard

AU - Heukamp, Lukas C

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Animals

KW - Biomarkers

KW - Carcinoma, Non-Small-Cell Lung

KW - Cell Line

KW - Disease Models, Animal

KW - Epithelial-Mesenchymal Transition

KW - Gene Expression Regulation, Neoplastic

KW - Gene Order

KW - Gene Targeting

KW - Genes, ras

KW - Humans

KW - Keratins

KW - Lung Neoplasms

KW - Mice

KW - Mice, Transgenic

KW - Small Cell Lung Carcinoma

U2 - 10.1371/journal.pone.0057996

DO - 10.1371/journal.pone.0057996

M3 - SCORING: Journal article

C2 - 23536778

VL - 8

SP - e57996

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 3

ER -