Adenomatous Polyposis Coli loss controls cell cycle regulators and response to paclitaxel in MDA-MB-157 metaplastic breast cancer cells.

Adenomatous Polyposis Coli (APC) is lost in approximately 70% of sporadic breast cancers, with an inclination towards triple negative breast cancer (TNBC). TNBC is treated with traditional chemotherapy, such as paclitaxel (PTX); however, tumors often develop drug resistance. We previously created AP...

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Autores principales:	Emily M Astarita, Sara M Maloney, Camden A Hoover, Bronwyn J Berkeley, Monica K VanKlompenberg, T Murlidharan Nair, Jenifer R Prosperi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/79747361a6854962ba0092eaf85574a0
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spelling	oai:doaj.org-article:79747361a6854962ba0092eaf85574a02021-12-02T20:19:38ZAdenomatous Polyposis Coli loss controls cell cycle regulators and response to paclitaxel in MDA-MB-157 metaplastic breast cancer cells.1932-620310.1371/journal.pone.0255738https://doaj.org/article/79747361a6854962ba0092eaf85574a02021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0255738https://doaj.org/toc/1932-6203Adenomatous Polyposis Coli (APC) is lost in approximately 70% of sporadic breast cancers, with an inclination towards triple negative breast cancer (TNBC). TNBC is treated with traditional chemotherapy, such as paclitaxel (PTX); however, tumors often develop drug resistance. We previously created APC knockdown cells (APC shRNA1) using the human TNBC cells, MDA-MB-157, and showed that APC loss induces PTX resistance. To understand the mechanisms behind APC-mediated PTX response, we performed cell cycle analysis and analyzed cell cycle related proteins. Cell cycle analysis indicated increased G2/M population in both PTX-treated APC shRNA1 and parental cells, suggesting that APC expression does not alter PTX-induced G2/M arrest. We further studied the subcellular localization of the G2/M transition proteins, cyclin B1 and CDK1. The APC shRNA1 cells had increased CDK1, which was preferentially localized to the cytoplasm, and increased baseline CDK6. RNA-sequencing was performed to gain a global understanding of changes downstream of APC loss and identified a broad mis-regulation of cell cycle-related genes in APC shRNA1 cells. Our studies are the first to show an interaction between APC and taxane response in breast cancer. The implications include designing combination therapy to re-sensitize APC-mutant breast cancers to taxanes using the specific cell cycle alterations.Emily M AstaritaSara M MaloneyCamden A HooverBronwyn J BerkeleyMonica K VanKlompenbergT Murlidharan NairJenifer R ProsperiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0255738 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Emily M Astarita Sara M Maloney Camden A Hoover Bronwyn J Berkeley Monica K VanKlompenberg T Murlidharan Nair Jenifer R Prosperi Adenomatous Polyposis Coli loss controls cell cycle regulators and response to paclitaxel in MDA-MB-157 metaplastic breast cancer cells.
description	Adenomatous Polyposis Coli (APC) is lost in approximately 70% of sporadic breast cancers, with an inclination towards triple negative breast cancer (TNBC). TNBC is treated with traditional chemotherapy, such as paclitaxel (PTX); however, tumors often develop drug resistance. We previously created APC knockdown cells (APC shRNA1) using the human TNBC cells, MDA-MB-157, and showed that APC loss induces PTX resistance. To understand the mechanisms behind APC-mediated PTX response, we performed cell cycle analysis and analyzed cell cycle related proteins. Cell cycle analysis indicated increased G2/M population in both PTX-treated APC shRNA1 and parental cells, suggesting that APC expression does not alter PTX-induced G2/M arrest. We further studied the subcellular localization of the G2/M transition proteins, cyclin B1 and CDK1. The APC shRNA1 cells had increased CDK1, which was preferentially localized to the cytoplasm, and increased baseline CDK6. RNA-sequencing was performed to gain a global understanding of changes downstream of APC loss and identified a broad mis-regulation of cell cycle-related genes in APC shRNA1 cells. Our studies are the first to show an interaction between APC and taxane response in breast cancer. The implications include designing combination therapy to re-sensitize APC-mutant breast cancers to taxanes using the specific cell cycle alterations.
format	article
author	Emily M Astarita Sara M Maloney Camden A Hoover Bronwyn J Berkeley Monica K VanKlompenberg T Murlidharan Nair Jenifer R Prosperi
author_facet	Emily M Astarita Sara M Maloney Camden A Hoover Bronwyn J Berkeley Monica K VanKlompenberg T Murlidharan Nair Jenifer R Prosperi
author_sort	Emily M Astarita
title	Adenomatous Polyposis Coli loss controls cell cycle regulators and response to paclitaxel in MDA-MB-157 metaplastic breast cancer cells.
title_short	Adenomatous Polyposis Coli loss controls cell cycle regulators and response to paclitaxel in MDA-MB-157 metaplastic breast cancer cells.
title_full	Adenomatous Polyposis Coli loss controls cell cycle regulators and response to paclitaxel in MDA-MB-157 metaplastic breast cancer cells.
title_fullStr	Adenomatous Polyposis Coli loss controls cell cycle regulators and response to paclitaxel in MDA-MB-157 metaplastic breast cancer cells.
title_full_unstemmed	Adenomatous Polyposis Coli loss controls cell cycle regulators and response to paclitaxel in MDA-MB-157 metaplastic breast cancer cells.
title_sort	adenomatous polyposis coli loss controls cell cycle regulators and response to paclitaxel in mda-mb-157 metaplastic breast cancer cells.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/79747361a6854962ba0092eaf85574a0
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Adenomatous Polyposis Coli loss controls cell cycle regulators and response to paclitaxel in MDA-MB-157 metaplastic breast cancer cells.

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