Cargando…
Doublecortin-like kinase 1 compromises DNA repair and induces chromosomal instability
Doublecortin-like kinase 1 (DCLK1) is a serine/threonine-kinase with two doublecortin (DCX) domains. DCLK1 is associated with microtubules via DCX domains and regulates microtubule polymerization. DCLK1 is known to be expressed in cancer stem cells and provides cancer cells with tumor-initiating cap...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6216093/ https://www.ncbi.nlm.nih.gov/pubmed/30417131 http://dx.doi.org/10.1016/j.bbrep.2018.10.014 |
_version_ | 1783368279289495552 |
---|---|
author | Lu, Yuxiong Maruyama, Junichi Kuwata, Keiko Fukuda, Hiroyuki Iwasa, Hiroaki Arimoto-Matsuzaki, Kyoko Sugimura, Haruhiko Hata, Yutaka |
author_facet | Lu, Yuxiong Maruyama, Junichi Kuwata, Keiko Fukuda, Hiroyuki Iwasa, Hiroaki Arimoto-Matsuzaki, Kyoko Sugimura, Haruhiko Hata, Yutaka |
author_sort | Lu, Yuxiong |
collection | PubMed |
description | Doublecortin-like kinase 1 (DCLK1) is a serine/threonine-kinase with two doublecortin (DCX) domains. DCLK1 is associated with microtubules via DCX domains and regulates microtubule polymerization. DCLK1 is known to be expressed in cancer stem cells and provides cancer cells with tumor-initiating capacity. Accumulating clinical evidence supports that DCLK1 is associated with tumor aggressiveness and is an important prognostic marker in various human cancers. However, the mechanism, by which DCLK1 causes oncogenesis, is not yet elucidated. In this study, we showed that DCLK1 empowers human mammary epithelial MCF10A cells to form spheres under floating condition in serum-free medium, which are reminiscent of mammospheres formed by mammary epithelial stem cells. We demonstrated that DCLK1 causes chromatin instability in MCF10A cells. DCLK1 impairs DNA repairs in human colon cancer HCT116 and lung cancer H1299 cells. The kinase-negative DCLK1 mutant and the mutant that is not associated with microtubules compromise DNA repair. In conclusion, DCLK1 interferes with DNA repair and induces tumorigenesis through genomic instability and this function is independent of the kinase activity and the regulation of microtubules. |
format | Online Article Text |
id | pubmed-6216093 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-62160932018-11-09 Doublecortin-like kinase 1 compromises DNA repair and induces chromosomal instability Lu, Yuxiong Maruyama, Junichi Kuwata, Keiko Fukuda, Hiroyuki Iwasa, Hiroaki Arimoto-Matsuzaki, Kyoko Sugimura, Haruhiko Hata, Yutaka Biochem Biophys Rep Research Article Doublecortin-like kinase 1 (DCLK1) is a serine/threonine-kinase with two doublecortin (DCX) domains. DCLK1 is associated with microtubules via DCX domains and regulates microtubule polymerization. DCLK1 is known to be expressed in cancer stem cells and provides cancer cells with tumor-initiating capacity. Accumulating clinical evidence supports that DCLK1 is associated with tumor aggressiveness and is an important prognostic marker in various human cancers. However, the mechanism, by which DCLK1 causes oncogenesis, is not yet elucidated. In this study, we showed that DCLK1 empowers human mammary epithelial MCF10A cells to form spheres under floating condition in serum-free medium, which are reminiscent of mammospheres formed by mammary epithelial stem cells. We demonstrated that DCLK1 causes chromatin instability in MCF10A cells. DCLK1 impairs DNA repairs in human colon cancer HCT116 and lung cancer H1299 cells. The kinase-negative DCLK1 mutant and the mutant that is not associated with microtubules compromise DNA repair. In conclusion, DCLK1 interferes with DNA repair and induces tumorigenesis through genomic instability and this function is independent of the kinase activity and the regulation of microtubules. Elsevier 2018-10-30 /pmc/articles/PMC6216093/ /pubmed/30417131 http://dx.doi.org/10.1016/j.bbrep.2018.10.014 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Lu, Yuxiong Maruyama, Junichi Kuwata, Keiko Fukuda, Hiroyuki Iwasa, Hiroaki Arimoto-Matsuzaki, Kyoko Sugimura, Haruhiko Hata, Yutaka Doublecortin-like kinase 1 compromises DNA repair and induces chromosomal instability |
title | Doublecortin-like kinase 1 compromises DNA repair and induces chromosomal instability |
title_full | Doublecortin-like kinase 1 compromises DNA repair and induces chromosomal instability |
title_fullStr | Doublecortin-like kinase 1 compromises DNA repair and induces chromosomal instability |
title_full_unstemmed | Doublecortin-like kinase 1 compromises DNA repair and induces chromosomal instability |
title_short | Doublecortin-like kinase 1 compromises DNA repair and induces chromosomal instability |
title_sort | doublecortin-like kinase 1 compromises dna repair and induces chromosomal instability |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6216093/ https://www.ncbi.nlm.nih.gov/pubmed/30417131 http://dx.doi.org/10.1016/j.bbrep.2018.10.014 |
work_keys_str_mv | AT luyuxiong doublecortinlikekinase1compromisesdnarepairandinduceschromosomalinstability AT maruyamajunichi doublecortinlikekinase1compromisesdnarepairandinduceschromosomalinstability AT kuwatakeiko doublecortinlikekinase1compromisesdnarepairandinduceschromosomalinstability AT fukudahiroyuki doublecortinlikekinase1compromisesdnarepairandinduceschromosomalinstability AT iwasahiroaki doublecortinlikekinase1compromisesdnarepairandinduceschromosomalinstability AT arimotomatsuzakikyoko doublecortinlikekinase1compromisesdnarepairandinduceschromosomalinstability AT sugimuraharuhiko doublecortinlikekinase1compromisesdnarepairandinduceschromosomalinstability AT hatayutaka doublecortinlikekinase1compromisesdnarepairandinduceschromosomalinstability |