Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype

Detalhes bibliográficos
Autor(a) principal: Silveira, W. A. da
Data de Publicação: 2017
Outros Autores: Palma, P. V. B., Sicchieri, R. D., Villacis, R. A. R., Mandarano, L. R. M., Oliveira, T. M. G., Antonio, H. M. R., Andrade, J. M., Muglia, V. F., Rogatto, S. R. [UNESP], Theillet, C., du Manoir, S., Tiezzi, D. G.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1038/s41598-017-02761-6
http://hdl.handle.net/11449/162859
Resumo: Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis from putative bCSC and reverse engineering of transcription control networks, we identified two networks associated with this phenotype. One controlled by SNAI2, TWIST1, BNC2, PRRX1 and TBX5 drives a mesenchymal or CSC-like phenotype. The second network is controlled by the SCML4, ZNF831, SP140 and IKZF3 transcription factors which correspond to immune response modulators. Immune response network expression is correlated with pathological response to chemotherapy, and in the Basal subtype is related to better recurrence-free survival. In patient-derived xenografts, the expression of these networks in patient tumours is predictive of engraftment success. Our findings point out a potential molecular mechanism underlying the balance between immune surveillance and EMT activation in breast cancer. This molecular mechanism may be useful to the development of new target therapies.
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spelling Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtypeBreast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis from putative bCSC and reverse engineering of transcription control networks, we identified two networks associated with this phenotype. One controlled by SNAI2, TWIST1, BNC2, PRRX1 and TBX5 drives a mesenchymal or CSC-like phenotype. The second network is controlled by the SCML4, ZNF831, SP140 and IKZF3 transcription factors which correspond to immune response modulators. Immune response network expression is correlated with pathological response to chemotherapy, and in the Basal subtype is related to better recurrence-free survival. In patient-derived xenografts, the expression of these networks in patient tumours is predictive of engraftment success. Our findings point out a potential molecular mechanism underlying the balance between immune surveillance and EMT activation in breast cancer. This molecular mechanism may be useful to the development of new target therapies.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)INCa grant MOPRECLIINCa grant Role of cancer stem cells during metastatic progression of breast cancerComprehensive Cancer Center of Montpellier (SIRIC Montpellier-Cancer)Univ Sao Paulo, Ribeirao Preto Med Sch, Ribeirao Preto, BrazilINSERM U1194, F-34298 Montpellier 5, FranceCtr Cell Therapy & Reg Blood Ctr, Natl Inst Sci & Technol Stem Cell & Cell Therapy, Ribeirao Preto, BrazilVejle Sygehus, Dept Clin Genet, Vejle, DenmarkUniv Southern Denmark, Inst Reg Hlth, Odense, DenmarkUniv Brasilia UnB, Inst Biol Sci, Dept Genet & Morphol, Brasilia, DF, BrazilSao Paulo State Univ, Dept Urol, Fac Med, UNESP, Botucatu, SP, BrazilUniv Montpellier, Inst Rech Cancerol Montpellier, F-34298 Montpellier 5, FranceICM, F-34298 Montpellier 5, FranceUniv Sao Paulo, Ribeirao Preto Med Sch, CISBi Ctr Integrat Syst Biol, Ribeirao Preto, BrazilSao Paulo State Univ, Dept Urol, Fac Med, UNESP, Botucatu, SP, BrazilFAPESP: 11/19758-5Nature Publishing GroupUniversidade de São Paulo (USP)INSERM U1194Ctr Cell Therapy & Reg Blood CtrVejle SygehusUniv Southern DenmarkUniversidade de Brasília (UnB)Universidade Estadual Paulista (Unesp)Univ MontpellierICMSilveira, W. A. daPalma, P. V. B.Sicchieri, R. D.Villacis, R. A. R.Mandarano, L. R. M.Oliveira, T. M. G.Antonio, H. M. R.Andrade, J. M.Muglia, V. F.Rogatto, S. R. [UNESP]Theillet, C.du Manoir, S.Tiezzi, D. G.2018-11-26T17:34:43Z2018-11-26T17:34:43Z2017-06-06info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article13application/pdfhttp://dx.doi.org/10.1038/s41598-017-02761-6Scientific Reports. London: Nature Publishing Group, v. 7, 13 p., 2017.2045-2322http://hdl.handle.net/11449/16285910.1038/s41598-017-02761-6WOS:000402771200002WOS000402771200002.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengScientific Reports1,533info:eu-repo/semantics/openAccess2024-09-03T14:29:59Zoai:repositorio.unesp.br:11449/162859Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T14:29:59Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype
title Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype
spellingShingle Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype
Silveira, W. A. da
title_short Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype
title_full Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype
title_fullStr Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype
title_full_unstemmed Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype
title_sort Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype
author Silveira, W. A. da
author_facet Silveira, W. A. da
Palma, P. V. B.
Sicchieri, R. D.
Villacis, R. A. R.
Mandarano, L. R. M.
Oliveira, T. M. G.
Antonio, H. M. R.
Andrade, J. M.
Muglia, V. F.
Rogatto, S. R. [UNESP]
Theillet, C.
du Manoir, S.
Tiezzi, D. G.
author_role author
author2 Palma, P. V. B.
Sicchieri, R. D.
Villacis, R. A. R.
Mandarano, L. R. M.
Oliveira, T. M. G.
Antonio, H. M. R.
Andrade, J. M.
Muglia, V. F.
Rogatto, S. R. [UNESP]
Theillet, C.
du Manoir, S.
Tiezzi, D. G.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
INSERM U1194
Ctr Cell Therapy & Reg Blood Ctr
Vejle Sygehus
Univ Southern Denmark
Universidade de Brasília (UnB)
Universidade Estadual Paulista (Unesp)
Univ Montpellier
ICM
dc.contributor.author.fl_str_mv Silveira, W. A. da
Palma, P. V. B.
Sicchieri, R. D.
Villacis, R. A. R.
Mandarano, L. R. M.
Oliveira, T. M. G.
Antonio, H. M. R.
Andrade, J. M.
Muglia, V. F.
Rogatto, S. R. [UNESP]
Theillet, C.
du Manoir, S.
Tiezzi, D. G.
description Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis from putative bCSC and reverse engineering of transcription control networks, we identified two networks associated with this phenotype. One controlled by SNAI2, TWIST1, BNC2, PRRX1 and TBX5 drives a mesenchymal or CSC-like phenotype. The second network is controlled by the SCML4, ZNF831, SP140 and IKZF3 transcription factors which correspond to immune response modulators. Immune response network expression is correlated with pathological response to chemotherapy, and in the Basal subtype is related to better recurrence-free survival. In patient-derived xenografts, the expression of these networks in patient tumours is predictive of engraftment success. Our findings point out a potential molecular mechanism underlying the balance between immune surveillance and EMT activation in breast cancer. This molecular mechanism may be useful to the development of new target therapies.
publishDate 2017
dc.date.none.fl_str_mv 2017-06-06
2018-11-26T17:34:43Z
2018-11-26T17:34:43Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1038/s41598-017-02761-6
Scientific Reports. London: Nature Publishing Group, v. 7, 13 p., 2017.
2045-2322
http://hdl.handle.net/11449/162859
10.1038/s41598-017-02761-6
WOS:000402771200002
WOS000402771200002.pdf
url http://dx.doi.org/10.1038/s41598-017-02761-6
http://hdl.handle.net/11449/162859
identifier_str_mv Scientific Reports. London: Nature Publishing Group, v. 7, 13 p., 2017.
2045-2322
10.1038/s41598-017-02761-6
WOS:000402771200002
WOS000402771200002.pdf
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Scientific Reports
1,533
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Web of Science
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv repositoriounesp@unesp.br
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