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LATS1/2 kinases trigger self-renewal of cancer stem cells in aggressive oral cancer

Cancer stem cells (CSCs), which play important roles in tumor initiation and progression, are resistant to many types of therapies. However, the regulatory mechanisms underlying CSC-specific properties, including self-renewal, are poorly understood. Here, we found that LATS1/2, the core Hippo pathwa...

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Autores principales: Nozaki, Masami, Yabuta, Norikazu, Fukuzawa, Moe, Mukai, Satomi, Okamoto, Ayumi, Sasakura, Towa, Fukushima, Kohshiro, Naito, Yoko, Longmore, Gregory D., Nojima, Hiroshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383686/
https://www.ncbi.nlm.nih.gov/pubmed/30800215
http://dx.doi.org/10.18632/oncotarget.26583
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author Nozaki, Masami
Yabuta, Norikazu
Fukuzawa, Moe
Mukai, Satomi
Okamoto, Ayumi
Sasakura, Towa
Fukushima, Kohshiro
Naito, Yoko
Longmore, Gregory D.
Nojima, Hiroshi
author_facet Nozaki, Masami
Yabuta, Norikazu
Fukuzawa, Moe
Mukai, Satomi
Okamoto, Ayumi
Sasakura, Towa
Fukushima, Kohshiro
Naito, Yoko
Longmore, Gregory D.
Nojima, Hiroshi
author_sort Nozaki, Masami
collection PubMed
description Cancer stem cells (CSCs), which play important roles in tumor initiation and progression, are resistant to many types of therapies. However, the regulatory mechanisms underlying CSC-specific properties, including self-renewal, are poorly understood. Here, we found that LATS1/2, the core Hippo pathway-kinases, were highly expressed in the oral squamous cell carcinoma line SAS, which exhibits high capacity of CSCs, and that depletion of these kinases prevented SAS cells from forming spheres under serum-free conditions. Detailed examination of the expression and activation of LATS kinases and related proteins over a time course of sphere formation revealed that LATS1/2 were more highly expressed and markedly activated before initiation of self-renewal. Moreover, TAZ, SNAIL, CHK1/2, and Aurora-A were expressed in hierarchical, oscillating patterns during sphere formation, suggesting that the process consists of four sequential steps. Our results indicate that LATS1/2 trigger self-renewal of CSCs by regulating the Hippo pathway, the EMT, and cell division.
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spelling pubmed-63836862019-02-23 LATS1/2 kinases trigger self-renewal of cancer stem cells in aggressive oral cancer Nozaki, Masami Yabuta, Norikazu Fukuzawa, Moe Mukai, Satomi Okamoto, Ayumi Sasakura, Towa Fukushima, Kohshiro Naito, Yoko Longmore, Gregory D. Nojima, Hiroshi Oncotarget Priority Research Paper Cancer stem cells (CSCs), which play important roles in tumor initiation and progression, are resistant to many types of therapies. However, the regulatory mechanisms underlying CSC-specific properties, including self-renewal, are poorly understood. Here, we found that LATS1/2, the core Hippo pathway-kinases, were highly expressed in the oral squamous cell carcinoma line SAS, which exhibits high capacity of CSCs, and that depletion of these kinases prevented SAS cells from forming spheres under serum-free conditions. Detailed examination of the expression and activation of LATS kinases and related proteins over a time course of sphere formation revealed that LATS1/2 were more highly expressed and markedly activated before initiation of self-renewal. Moreover, TAZ, SNAIL, CHK1/2, and Aurora-A were expressed in hierarchical, oscillating patterns during sphere formation, suggesting that the process consists of four sequential steps. Our results indicate that LATS1/2 trigger self-renewal of CSCs by regulating the Hippo pathway, the EMT, and cell division. Impact Journals LLC 2019-02-01 /pmc/articles/PMC6383686/ /pubmed/30800215 http://dx.doi.org/10.18632/oncotarget.26583 Text en Copyright: © 2019 Nozaki et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Priority Research Paper
Nozaki, Masami
Yabuta, Norikazu
Fukuzawa, Moe
Mukai, Satomi
Okamoto, Ayumi
Sasakura, Towa
Fukushima, Kohshiro
Naito, Yoko
Longmore, Gregory D.
Nojima, Hiroshi
LATS1/2 kinases trigger self-renewal of cancer stem cells in aggressive oral cancer
title LATS1/2 kinases trigger self-renewal of cancer stem cells in aggressive oral cancer
title_full LATS1/2 kinases trigger self-renewal of cancer stem cells in aggressive oral cancer
title_fullStr LATS1/2 kinases trigger self-renewal of cancer stem cells in aggressive oral cancer
title_full_unstemmed LATS1/2 kinases trigger self-renewal of cancer stem cells in aggressive oral cancer
title_short LATS1/2 kinases trigger self-renewal of cancer stem cells in aggressive oral cancer
title_sort lats1/2 kinases trigger self-renewal of cancer stem cells in aggressive oral cancer
topic Priority Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383686/
https://www.ncbi.nlm.nih.gov/pubmed/30800215
http://dx.doi.org/10.18632/oncotarget.26583
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