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The ATM and ATR kinases regulate centrosome clustering and tumor recurrence by targeting KIFC1 phosphorylation

Drug resistance and tumor recurrence are major challenges in cancer treatment. Cancer cells often display centrosome amplification. To maintain survival, cancer cells achieve bipolar division by clustering supernumerary centrosomes. Targeting centrosome clustering is therefore considered a promising...

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Autores principales: Fan, Guangjian, Sun, Lianhui, Meng, Ling, Hu, Chen, Wang, Xing, Shi, Zhan, Hu, Congli, Han, Yang, Yang, Qingqing, Cao, Liu, Zhang, Xiaohong, Zhang, Yan, Song, Xianmin, Xia, Shujie, He, Baokun, Zhang, Shengping, Wang, Chuangui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782532/
https://www.ncbi.nlm.nih.gov/pubmed/33397932
http://dx.doi.org/10.1038/s41467-020-20208-x
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author Fan, Guangjian
Sun, Lianhui
Meng, Ling
Hu, Chen
Wang, Xing
Shi, Zhan
Hu, Congli
Han, Yang
Yang, Qingqing
Cao, Liu
Zhang, Xiaohong
Zhang, Yan
Song, Xianmin
Xia, Shujie
He, Baokun
Zhang, Shengping
Wang, Chuangui
author_facet Fan, Guangjian
Sun, Lianhui
Meng, Ling
Hu, Chen
Wang, Xing
Shi, Zhan
Hu, Congli
Han, Yang
Yang, Qingqing
Cao, Liu
Zhang, Xiaohong
Zhang, Yan
Song, Xianmin
Xia, Shujie
He, Baokun
Zhang, Shengping
Wang, Chuangui
author_sort Fan, Guangjian
collection PubMed
description Drug resistance and tumor recurrence are major challenges in cancer treatment. Cancer cells often display centrosome amplification. To maintain survival, cancer cells achieve bipolar division by clustering supernumerary centrosomes. Targeting centrosome clustering is therefore considered a promising therapeutic strategy. However, the regulatory mechanisms of centrosome clustering remain unclear. Here we report that KIFC1, a centrosome clustering regulator, is positively associated with tumor recurrence. Under DNA damaging treatments, the ATM and ATR kinases phosphorylate KIFC1 at Ser26 to selectively maintain the survival of cancer cells with amplified centrosomes via centrosome clustering, leading to drug resistance and tumor recurrence. Inhibition of KIFC1 phosphorylation represses centrosome clustering and tumor recurrence. This study identified KIFC1 as a prognostic tumor recurrence marker, and revealed that tumors can acquire therapeutic resistance and recurrence via triggering centrosome clustering under DNA damage stresses, suggesting that blocking KIFC1 phosphorylation may open a new vista for cancer therapy.
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spelling pubmed-77825322021-01-11 The ATM and ATR kinases regulate centrosome clustering and tumor recurrence by targeting KIFC1 phosphorylation Fan, Guangjian Sun, Lianhui Meng, Ling Hu, Chen Wang, Xing Shi, Zhan Hu, Congli Han, Yang Yang, Qingqing Cao, Liu Zhang, Xiaohong Zhang, Yan Song, Xianmin Xia, Shujie He, Baokun Zhang, Shengping Wang, Chuangui Nat Commun Article Drug resistance and tumor recurrence are major challenges in cancer treatment. Cancer cells often display centrosome amplification. To maintain survival, cancer cells achieve bipolar division by clustering supernumerary centrosomes. Targeting centrosome clustering is therefore considered a promising therapeutic strategy. However, the regulatory mechanisms of centrosome clustering remain unclear. Here we report that KIFC1, a centrosome clustering regulator, is positively associated with tumor recurrence. Under DNA damaging treatments, the ATM and ATR kinases phosphorylate KIFC1 at Ser26 to selectively maintain the survival of cancer cells with amplified centrosomes via centrosome clustering, leading to drug resistance and tumor recurrence. Inhibition of KIFC1 phosphorylation represses centrosome clustering and tumor recurrence. This study identified KIFC1 as a prognostic tumor recurrence marker, and revealed that tumors can acquire therapeutic resistance and recurrence via triggering centrosome clustering under DNA damage stresses, suggesting that blocking KIFC1 phosphorylation may open a new vista for cancer therapy. Nature Publishing Group UK 2021-01-04 /pmc/articles/PMC7782532/ /pubmed/33397932 http://dx.doi.org/10.1038/s41467-020-20208-x Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Fan, Guangjian
Sun, Lianhui
Meng, Ling
Hu, Chen
Wang, Xing
Shi, Zhan
Hu, Congli
Han, Yang
Yang, Qingqing
Cao, Liu
Zhang, Xiaohong
Zhang, Yan
Song, Xianmin
Xia, Shujie
He, Baokun
Zhang, Shengping
Wang, Chuangui
The ATM and ATR kinases regulate centrosome clustering and tumor recurrence by targeting KIFC1 phosphorylation
title The ATM and ATR kinases regulate centrosome clustering and tumor recurrence by targeting KIFC1 phosphorylation
title_full The ATM and ATR kinases regulate centrosome clustering and tumor recurrence by targeting KIFC1 phosphorylation
title_fullStr The ATM and ATR kinases regulate centrosome clustering and tumor recurrence by targeting KIFC1 phosphorylation
title_full_unstemmed The ATM and ATR kinases regulate centrosome clustering and tumor recurrence by targeting KIFC1 phosphorylation
title_short The ATM and ATR kinases regulate centrosome clustering and tumor recurrence by targeting KIFC1 phosphorylation
title_sort atm and atr kinases regulate centrosome clustering and tumor recurrence by targeting kifc1 phosphorylation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782532/
https://www.ncbi.nlm.nih.gov/pubmed/33397932
http://dx.doi.org/10.1038/s41467-020-20208-x
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