RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer

Autores
Fernández, Natalia Brenda; Sosa, Sofía María; Roberts, Justin T.; Recouvreux, María Sol; Rocha Viegas, Luciana; Christenson, Jessica; Spoelstra, Nicole; Couto, Facundo Luis; Raimondi, Ana Rosa; Richer, Jennifer K.; Rubinstein, Natalia
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype for which no effective targeted therapies are available. Growing evidence suggests that chemotherapy-resistant cancer cells with stem-like properties (CSC) may repopulate the tumor. Androgen receptor (AR) is expressed in up to 50% of TNBC, and AR inhibition decreases CSC and tumor initiation. Runt-related transcription factor 1 (RUNX1) correlates with poor prognosis in TNBC and is regulated by AR in prostate cancer. Our group has shown that RUNX1 promotes TNBC cell migration and regulates tumor gene expression. We hypothesized that RUNX1 is regulated by AR and that both may work together in TNBC CSC to promote disease recurrence following chemotherapy. Results and methods: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) experiments in MDA-MB-453 revealed AR binding to RUNX1 regulatory regions. RUNX1 expression is upregulated by dihydrotestosterone (DHT) in MDA-MB-453 and in HCI-009 patient-derived xenograft (PDX) tumors (p<0.05). RUNX1 is increased in a CSC-like experimental model in MDA-MB-453 and SUM-159PT cells (p<0.05). Inhibition of RUNX1 transcriptional activity reduced the expression of CSC markers. Interestingly, RUNX1 inhibition reduced cell viability and enhanced paclitaxel and enzalutamide sensitivity. Conclusion: Targeting RUNX1 may be an attractive strategy to potentiate the anti-tumor effects of AR inhibition, specifically in the slow growing CSC-like populations that resist chemotherapy leading to metastatic disease.
Fil: Fernández, Natalia Brenda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina
Fil: Sosa, Sofía María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina
Fil: Roberts, Justin T.. University Of South Alabama; Estados Unidos
Fil: Recouvreux, María Sol. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina. University of California; Estados Unidos
Fil: Rocha Viegas, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Christenson, Jessica. University of Colorado; Estados Unidos
Fil: Spoelstra, Nicole. University of Colorado; Estados Unidos
Fil: Couto, Facundo Luis. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina
Fil: Raimondi, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Richer, Jennifer K.. University of Colorado; Estados Unidos
Fil: Rubinstein, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina
Materia
RUNX1
AR
CSC
TNBC
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/230540
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/230540
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancerFernández, Natalia BrendaSosa, Sofía MaríaRoberts, Justin T.Recouvreux, María SolRocha Viegas, LucianaChristenson, JessicaSpoelstra, NicoleCouto, Facundo LuisRaimondi, Ana RosaRicher, Jennifer K.Rubinstein, NataliaRUNX1ARCSCTNBChttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype for which no effective targeted therapies are available. Growing evidence suggests that chemotherapy-resistant cancer cells with stem-like properties (CSC) may repopulate the tumor. Androgen receptor (AR) is expressed in up to 50% of TNBC, and AR inhibition decreases CSC and tumor initiation. Runt-related transcription factor 1 (RUNX1) correlates with poor prognosis in TNBC and is regulated by AR in prostate cancer. Our group has shown that RUNX1 promotes TNBC cell migration and regulates tumor gene expression. We hypothesized that RUNX1 is regulated by AR and that both may work together in TNBC CSC to promote disease recurrence following chemotherapy. Results and methods: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) experiments in MDA-MB-453 revealed AR binding to RUNX1 regulatory regions. RUNX1 expression is upregulated by dihydrotestosterone (DHT) in MDA-MB-453 and in HCI-009 patient-derived xenograft (PDX) tumors (p<0.05). RUNX1 is increased in a CSC-like experimental model in MDA-MB-453 and SUM-159PT cells (p<0.05). Inhibition of RUNX1 transcriptional activity reduced the expression of CSC markers. Interestingly, RUNX1 inhibition reduced cell viability and enhanced paclitaxel and enzalutamide sensitivity. Conclusion: Targeting RUNX1 may be an attractive strategy to potentiate the anti-tumor effects of AR inhibition, specifically in the slow growing CSC-like populations that resist chemotherapy leading to metastatic disease.Fil: Fernández, Natalia Brenda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; ArgentinaFil: Sosa, Sofía María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; ArgentinaFil: Roberts, Justin T.. University Of South Alabama; Estados UnidosFil: Recouvreux, María Sol. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina. University of California; Estados UnidosFil: Rocha Viegas, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Christenson, Jessica. University of Colorado; Estados UnidosFil: Spoelstra, Nicole. University of Colorado; Estados UnidosFil: Couto, Facundo Luis. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; ArgentinaFil: Raimondi, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Richer, Jennifer K.. University of Colorado; Estados UnidosFil: Rubinstein, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; ArgentinaCold Spring Harbor Laboratory Press2022-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/230540Fernández, Natalia Brenda; Sosa, Sofía María; Roberts, Justin T.; Recouvreux, María Sol; Rocha Viegas, Luciana; et al.; RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer; Cold Spring Harbor Laboratory Press; BioRxiv; 2022; 11-2022; 1-232692-8205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2022.11.12.516193v1info:eu-repo/semantics/altIdentifier/doi/10.1101/2022.11.12.516193info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:58:03Zoai:ri.conicet.gov.ar:11336/230540instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:58:04.203CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer
title RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer
spellingShingle RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer
Fernández, Natalia Brenda
RUNX1
AR
CSC
TNBC
title_short RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer
title_full RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer
title_fullStr RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer
title_full_unstemmed RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer
title_sort RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer
dc.creator.none.fl_str_mv Fernández, Natalia Brenda
Sosa, Sofía María
Roberts, Justin T.
Recouvreux, María Sol
Rocha Viegas, Luciana
Christenson, Jessica
Spoelstra, Nicole
Couto, Facundo Luis
Raimondi, Ana Rosa
Richer, Jennifer K.
Rubinstein, Natalia
author Fernández, Natalia Brenda
author_facet Fernández, Natalia Brenda
Sosa, Sofía María
Roberts, Justin T.
Recouvreux, María Sol
Rocha Viegas, Luciana
Christenson, Jessica
Spoelstra, Nicole
Couto, Facundo Luis
Raimondi, Ana Rosa
Richer, Jennifer K.
Rubinstein, Natalia
author_role author
author2 Sosa, Sofía María
Roberts, Justin T.
Recouvreux, María Sol
Rocha Viegas, Luciana
Christenson, Jessica
Spoelstra, Nicole
Couto, Facundo Luis
Raimondi, Ana Rosa
Richer, Jennifer K.
Rubinstein, Natalia
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv RUNX1
AR
CSC
TNBC
topic RUNX1
AR
CSC
TNBC
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Background: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype for which no effective targeted therapies are available. Growing evidence suggests that chemotherapy-resistant cancer cells with stem-like properties (CSC) may repopulate the tumor. Androgen receptor (AR) is expressed in up to 50% of TNBC, and AR inhibition decreases CSC and tumor initiation. Runt-related transcription factor 1 (RUNX1) correlates with poor prognosis in TNBC and is regulated by AR in prostate cancer. Our group has shown that RUNX1 promotes TNBC cell migration and regulates tumor gene expression. We hypothesized that RUNX1 is regulated by AR and that both may work together in TNBC CSC to promote disease recurrence following chemotherapy. Results and methods: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) experiments in MDA-MB-453 revealed AR binding to RUNX1 regulatory regions. RUNX1 expression is upregulated by dihydrotestosterone (DHT) in MDA-MB-453 and in HCI-009 patient-derived xenograft (PDX) tumors (p<0.05). RUNX1 is increased in a CSC-like experimental model in MDA-MB-453 and SUM-159PT cells (p<0.05). Inhibition of RUNX1 transcriptional activity reduced the expression of CSC markers. Interestingly, RUNX1 inhibition reduced cell viability and enhanced paclitaxel and enzalutamide sensitivity. Conclusion: Targeting RUNX1 may be an attractive strategy to potentiate the anti-tumor effects of AR inhibition, specifically in the slow growing CSC-like populations that resist chemotherapy leading to metastatic disease.
Fil: Fernández, Natalia Brenda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina
Fil: Sosa, Sofía María. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina
Fil: Roberts, Justin T.. University Of South Alabama; Estados Unidos
Fil: Recouvreux, María Sol. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina. University of California; Estados Unidos
Fil: Rocha Viegas, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Christenson, Jessica. University of Colorado; Estados Unidos
Fil: Spoelstra, Nicole. University of Colorado; Estados Unidos
Fil: Couto, Facundo Luis. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina
Fil: Raimondi, Ana Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Richer, Jennifer K.. University of Colorado; Estados Unidos
Fil: Rubinstein, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biociencias, Biotecnología y Biología Traslacional.; Argentina
description Background: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype for which no effective targeted therapies are available. Growing evidence suggests that chemotherapy-resistant cancer cells with stem-like properties (CSC) may repopulate the tumor. Androgen receptor (AR) is expressed in up to 50% of TNBC, and AR inhibition decreases CSC and tumor initiation. Runt-related transcription factor 1 (RUNX1) correlates with poor prognosis in TNBC and is regulated by AR in prostate cancer. Our group has shown that RUNX1 promotes TNBC cell migration and regulates tumor gene expression. We hypothesized that RUNX1 is regulated by AR and that both may work together in TNBC CSC to promote disease recurrence following chemotherapy. Results and methods: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) experiments in MDA-MB-453 revealed AR binding to RUNX1 regulatory regions. RUNX1 expression is upregulated by dihydrotestosterone (DHT) in MDA-MB-453 and in HCI-009 patient-derived xenograft (PDX) tumors (p<0.05). RUNX1 is increased in a CSC-like experimental model in MDA-MB-453 and SUM-159PT cells (p<0.05). Inhibition of RUNX1 transcriptional activity reduced the expression of CSC markers. Interestingly, RUNX1 inhibition reduced cell viability and enhanced paclitaxel and enzalutamide sensitivity. Conclusion: Targeting RUNX1 may be an attractive strategy to potentiate the anti-tumor effects of AR inhibition, specifically in the slow growing CSC-like populations that resist chemotherapy leading to metastatic disease.
publishDate 2022
dc.date.none.fl_str_mv 2022-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/230540
Fernández, Natalia Brenda; Sosa, Sofía María; Roberts, Justin T.; Recouvreux, María Sol; Rocha Viegas, Luciana; et al.; RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer; Cold Spring Harbor Laboratory Press; BioRxiv; 2022; 11-2022; 1-23
2692-8205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/230540
identifier_str_mv Fernández, Natalia Brenda; Sosa, Sofía María; Roberts, Justin T.; Recouvreux, María Sol; Rocha Viegas, Luciana; et al.; RUNX1 is regulated by androgen receptor to promote cancer stem markers and chemotherapy resistance in triple negative breast cancer; Cold Spring Harbor Laboratory Press; BioRxiv; 2022; 11-2022; 1-23
2692-8205
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2022.11.12.516193v1
info:eu-repo/semantics/altIdentifier/doi/10.1101/2022.11.12.516193
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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