Depletion of Survivin suppresses docetaxel-induced apoptosis in HeLa cells by facilitating mitotic slippage

Abstract The anticancer effects of taxanes are attributed to the induction of mitotic arrest through activation of the spindle assembly checkpoint. Cell death following extended mitotic arrest is mediated by the intrinsic apoptosis pathway. Accordingly, factors that influence the robustness of mitot...

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Autores principales:	Teng-Long Han, Hang Sha, Jun Ji, Yun-Tian Li, Deng-Shan Wu, Hu Lin, Bin Hu, Zhi-Xin Jiang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/569d1d72d46642f7bde9fd7f54bd17a3
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spelling	oai:doaj.org-article:569d1d72d46642f7bde9fd7f54bd17a32021-12-02T14:16:26ZDepletion of Survivin suppresses docetaxel-induced apoptosis in HeLa cells by facilitating mitotic slippage10.1038/s41598-021-81563-32045-2322https://doaj.org/article/569d1d72d46642f7bde9fd7f54bd17a32021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81563-3https://doaj.org/toc/2045-2322Abstract The anticancer effects of taxanes are attributed to the induction of mitotic arrest through activation of the spindle assembly checkpoint. Cell death following extended mitotic arrest is mediated by the intrinsic apoptosis pathway. Accordingly, factors that influence the robustness of mitotic arrest or disrupt the apoptotic machinery confer drug resistance. Survivin is an inhibitor of apoptosis protein. Its overexpression is associated with chemoresistance, and its targeting leads to drug sensitization. However, Survivin also acts specifically in the spindle assembly checkpoint response to taxanes. Hence, the failure of Survivin-depleted cells to arrest in mitosis may lead to taxane resistance. Here we show that Survivin depletion protects HeLa cells against docetaxel-induced apoptosis by facilitating mitotic slippage. However, Survivin depletion does not promote clonogenic survival of tumor cells but increases the level of cellular senescence induced by docetaxel. Moreover, lentiviral overexpression of Survivin does not provide protection against docetaxel or cisplatin treatment, in contrast to the anti-apoptotic Bcl-xL or Bcl-2. Our findings suggest that targeting Survivin may influence the cell response to docetaxel by driving the cells through aberrant mitotic progression, rather than directly sensitizing cells to apoptosis.Teng-Long HanHang ShaJun JiYun-Tian LiDeng-Shan WuHu LinBin HuZhi-Xin JiangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Teng-Long Han Hang Sha Jun Ji Yun-Tian Li Deng-Shan Wu Hu Lin Bin Hu Zhi-Xin Jiang Depletion of Survivin suppresses docetaxel-induced apoptosis in HeLa cells by facilitating mitotic slippage
description	Abstract The anticancer effects of taxanes are attributed to the induction of mitotic arrest through activation of the spindle assembly checkpoint. Cell death following extended mitotic arrest is mediated by the intrinsic apoptosis pathway. Accordingly, factors that influence the robustness of mitotic arrest or disrupt the apoptotic machinery confer drug resistance. Survivin is an inhibitor of apoptosis protein. Its overexpression is associated with chemoresistance, and its targeting leads to drug sensitization. However, Survivin also acts specifically in the spindle assembly checkpoint response to taxanes. Hence, the failure of Survivin-depleted cells to arrest in mitosis may lead to taxane resistance. Here we show that Survivin depletion protects HeLa cells against docetaxel-induced apoptosis by facilitating mitotic slippage. However, Survivin depletion does not promote clonogenic survival of tumor cells but increases the level of cellular senescence induced by docetaxel. Moreover, lentiviral overexpression of Survivin does not provide protection against docetaxel or cisplatin treatment, in contrast to the anti-apoptotic Bcl-xL or Bcl-2. Our findings suggest that targeting Survivin may influence the cell response to docetaxel by driving the cells through aberrant mitotic progression, rather than directly sensitizing cells to apoptosis.
format	article
author	Teng-Long Han Hang Sha Jun Ji Yun-Tian Li Deng-Shan Wu Hu Lin Bin Hu Zhi-Xin Jiang
author_facet	Teng-Long Han Hang Sha Jun Ji Yun-Tian Li Deng-Shan Wu Hu Lin Bin Hu Zhi-Xin Jiang
author_sort	Teng-Long Han
title	Depletion of Survivin suppresses docetaxel-induced apoptosis in HeLa cells by facilitating mitotic slippage
title_short	Depletion of Survivin suppresses docetaxel-induced apoptosis in HeLa cells by facilitating mitotic slippage
title_full	Depletion of Survivin suppresses docetaxel-induced apoptosis in HeLa cells by facilitating mitotic slippage
title_fullStr	Depletion of Survivin suppresses docetaxel-induced apoptosis in HeLa cells by facilitating mitotic slippage
title_full_unstemmed	Depletion of Survivin suppresses docetaxel-induced apoptosis in HeLa cells by facilitating mitotic slippage
title_sort	depletion of survivin suppresses docetaxel-induced apoptosis in hela cells by facilitating mitotic slippage
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/569d1d72d46642f7bde9fd7f54bd17a3
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Depletion of Survivin suppresses docetaxel-induced apoptosis in HeLa cells by facilitating mitotic slippage

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