Modulation of SOX2 expression delineates an end-point for paclitaxel-effectiveness in breast cancer stem cells

Abstract Tumor relapse in triple negative breast cancer patients has been implicated to chemoresistant cancer stem cells (CSCs), which under favorable conditions culminate in tumor re-formation and metastasis. Hence, eradication of CSCs during systemic chemotherapy is imperative. CSCs were sorted us...

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Autores principales:	Pritha Mukherjee, Arnab Gupta, Dhrubajyoti Chattopadhyay, Urmi Chatterji
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/50cc4ab0478c48508109340cb314607b
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spelling	oai:doaj.org-article:50cc4ab0478c48508109340cb314607b2021-12-02T12:30:36ZModulation of SOX2 expression delineates an end-point for paclitaxel-effectiveness in breast cancer stem cells10.1038/s41598-017-08971-22045-2322https://doaj.org/article/50cc4ab0478c48508109340cb314607b2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08971-2https://doaj.org/toc/2045-2322Abstract Tumor relapse in triple negative breast cancer patients has been implicated to chemoresistant cancer stem cells (CSCs), which under favorable conditions culminate in tumor re-formation and metastasis. Hence, eradication of CSCs during systemic chemotherapy is imperative. CSCs were sorted using immuno-phenotyping and aldefluor assay. Gene expression profiling of normal breast stem cells and breast CSCs from chemo-treated patients were carried out. Silencing SOX2 was achieved by siRNA method. Mammosphere culture and wound healing assays were carried out to assess efficacy of CSCs. Microarray analysis revealed elevated expression of SOX2, ABCG2 and TWIST1, unraveling an intertwined pluripotency-chemoresistance-EMT axis. Although paclitaxel treatment led to temporary arrest of cell migration, invasiveness resumed after drug removal. The ‘twist in the tale’ was a consistently elevated expression of TWIST1, substantiating that TWIST1 can also promote stemness and chemoresistance in tumors; hence, its eradication was imperative. Silencing SOX2 increased chemo-sensitivity and diminished sphere formation, and led to TWIST1 down regulation. This study eventually established that SOX2 silencing of CSCs along with paclitaxel treatment reduced SOX2-ABCG2-TWIST1 expression, disrupted sphere forming capacity and also reduced invasiveness by retaining epithelial-like properties of the cells, thereby suggesting a more comprehensive therapy for TNBC patients in future.Pritha MukherjeeArnab GuptaDhrubajyoti ChattopadhyayUrmi ChatterjiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pritha Mukherjee Arnab Gupta Dhrubajyoti Chattopadhyay Urmi Chatterji Modulation of SOX2 expression delineates an end-point for paclitaxel-effectiveness in breast cancer stem cells
description	Abstract Tumor relapse in triple negative breast cancer patients has been implicated to chemoresistant cancer stem cells (CSCs), which under favorable conditions culminate in tumor re-formation and metastasis. Hence, eradication of CSCs during systemic chemotherapy is imperative. CSCs were sorted using immuno-phenotyping and aldefluor assay. Gene expression profiling of normal breast stem cells and breast CSCs from chemo-treated patients were carried out. Silencing SOX2 was achieved by siRNA method. Mammosphere culture and wound healing assays were carried out to assess efficacy of CSCs. Microarray analysis revealed elevated expression of SOX2, ABCG2 and TWIST1, unraveling an intertwined pluripotency-chemoresistance-EMT axis. Although paclitaxel treatment led to temporary arrest of cell migration, invasiveness resumed after drug removal. The ‘twist in the tale’ was a consistently elevated expression of TWIST1, substantiating that TWIST1 can also promote stemness and chemoresistance in tumors; hence, its eradication was imperative. Silencing SOX2 increased chemo-sensitivity and diminished sphere formation, and led to TWIST1 down regulation. This study eventually established that SOX2 silencing of CSCs along with paclitaxel treatment reduced SOX2-ABCG2-TWIST1 expression, disrupted sphere forming capacity and also reduced invasiveness by retaining epithelial-like properties of the cells, thereby suggesting a more comprehensive therapy for TNBC patients in future.
format	article
author	Pritha Mukherjee Arnab Gupta Dhrubajyoti Chattopadhyay Urmi Chatterji
author_facet	Pritha Mukherjee Arnab Gupta Dhrubajyoti Chattopadhyay Urmi Chatterji
author_sort	Pritha Mukherjee
title	Modulation of SOX2 expression delineates an end-point for paclitaxel-effectiveness in breast cancer stem cells
title_short	Modulation of SOX2 expression delineates an end-point for paclitaxel-effectiveness in breast cancer stem cells
title_full	Modulation of SOX2 expression delineates an end-point for paclitaxel-effectiveness in breast cancer stem cells
title_fullStr	Modulation of SOX2 expression delineates an end-point for paclitaxel-effectiveness in breast cancer stem cells
title_full_unstemmed	Modulation of SOX2 expression delineates an end-point for paclitaxel-effectiveness in breast cancer stem cells
title_sort	modulation of sox2 expression delineates an end-point for paclitaxel-effectiveness in breast cancer stem cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/50cc4ab0478c48508109340cb314607b
work_keys_str_mv	AT prithamukherjee modulationofsox2expressiondelineatesanendpointforpaclitaxeleffectivenessinbreastcancerstemcells AT arnabgupta modulationofsox2expressiondelineatesanendpointforpaclitaxeleffectivenessinbreastcancerstemcells AT dhrubajyotichattopadhyay modulationofsox2expressiondelineatesanendpointforpaclitaxeleffectivenessinbreastcancerstemcells AT urmichatterji modulationofsox2expressiondelineatesanendpointforpaclitaxeleffectivenessinbreastcancerstemcells
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Modulation of SOX2 expression delineates an end-point for paclitaxel-effectiveness in breast cancer stem cells

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