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The oncogene cyclin D1 promotes bipolar spindle integrity under compressive force

The mitotic spindle is the bipolar, microtubule-based structure that segregates chromosomes at each cell division. Aberrant spindles are frequently observed in cancer cells, but how oncogenic transformation affects spindle mechanics and function, particularly in the mechanical context of solid tumor...

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Autores principales: Sutanto, Renaldo, Neahring, Lila, Marques, Andrea Serra, Kilinc, Seda, Goga, Andrei, Dumont, Sophie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312523/
https://www.ncbi.nlm.nih.gov/pubmed/37398487
http://dx.doi.org/10.1101/2023.05.30.542893
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author Sutanto, Renaldo
Neahring, Lila
Marques, Andrea Serra
Kilinc, Seda
Goga, Andrei
Dumont, Sophie
author_facet Sutanto, Renaldo
Neahring, Lila
Marques, Andrea Serra
Kilinc, Seda
Goga, Andrei
Dumont, Sophie
author_sort Sutanto, Renaldo
collection PubMed
description The mitotic spindle is the bipolar, microtubule-based structure that segregates chromosomes at each cell division. Aberrant spindles are frequently observed in cancer cells, but how oncogenic transformation affects spindle mechanics and function, particularly in the mechanical context of solid tumors, remains poorly understood. Here, we constitutively overexpress the oncogene cyclin D1 in human MCF10A cells to probe its effects on spindle architecture and response to compressive force. We find that cyclin D1 overexpression increases the incidence of spindles with extra poles, centrioles, and chromosomes. However, it also protects spindle poles from fracturing under compressive force, a deleterious outcome linked to multipolar cell divisions. Our findings suggest that cyclin D1 overexpression may adapt cells to increased compressive stress, contributing to its prevalence in cancers such as breast cancer by allowing continued proliferation in mechanically challenging environments.
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spelling pubmed-103125232023-07-01 The oncogene cyclin D1 promotes bipolar spindle integrity under compressive force Sutanto, Renaldo Neahring, Lila Marques, Andrea Serra Kilinc, Seda Goga, Andrei Dumont, Sophie bioRxiv Article The mitotic spindle is the bipolar, microtubule-based structure that segregates chromosomes at each cell division. Aberrant spindles are frequently observed in cancer cells, but how oncogenic transformation affects spindle mechanics and function, particularly in the mechanical context of solid tumors, remains poorly understood. Here, we constitutively overexpress the oncogene cyclin D1 in human MCF10A cells to probe its effects on spindle architecture and response to compressive force. We find that cyclin D1 overexpression increases the incidence of spindles with extra poles, centrioles, and chromosomes. However, it also protects spindle poles from fracturing under compressive force, a deleterious outcome linked to multipolar cell divisions. Our findings suggest that cyclin D1 overexpression may adapt cells to increased compressive stress, contributing to its prevalence in cancers such as breast cancer by allowing continued proliferation in mechanically challenging environments. Cold Spring Harbor Laboratory 2023-05-31 /pmc/articles/PMC10312523/ /pubmed/37398487 http://dx.doi.org/10.1101/2023.05.30.542893 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Sutanto, Renaldo
Neahring, Lila
Marques, Andrea Serra
Kilinc, Seda
Goga, Andrei
Dumont, Sophie
The oncogene cyclin D1 promotes bipolar spindle integrity under compressive force
title The oncogene cyclin D1 promotes bipolar spindle integrity under compressive force
title_full The oncogene cyclin D1 promotes bipolar spindle integrity under compressive force
title_fullStr The oncogene cyclin D1 promotes bipolar spindle integrity under compressive force
title_full_unstemmed The oncogene cyclin D1 promotes bipolar spindle integrity under compressive force
title_short The oncogene cyclin D1 promotes bipolar spindle integrity under compressive force
title_sort oncogene cyclin d1 promotes bipolar spindle integrity under compressive force
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10312523/
https://www.ncbi.nlm.nih.gov/pubmed/37398487
http://dx.doi.org/10.1101/2023.05.30.542893
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