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

Autor: da Silveira WA; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; INSERM U1194, 34298 Montpellier cedex 5, Montpellier, France., Palma PVB; National Institute of Science and Technology in Stem Cell and Cell Therapy, Center for Cell Therapy and Regional Blood Center, Ribeirao Preto, Brazil., Sicchieri RD; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Villacis RAR; Department of Genetics and Morphology, Institute of Biological Sciences, University of Brasília - UnB, Brasília, DF, Brazil., Mandarano LRM; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Oliveira TMG; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Antonio HMR; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Andrade JM; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Muglia VF; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Rogatto SR; Department of Clinical Genetics, Vejle Sygehus, Vejle, and Institute of Regional Health, University of Southern, Denmark, Denmark.; Department of Urology, Faculty of Medicine, UNESP, Sao Paulo State University, Botucatu, Sao Paulo, Brazil., Theillet C; INSERM U1194, 34298 Montpellier cedex 5, Montpellier, France.; Institut de Recherche en Cancérologie de Montpellier, Université de Montpellier, 34298 Montpellier cedex 5, Montpellier, France.; Institut de Cancérologie de Montpellier (ICM), 34298 Montpellier cedex 5, Montpellier, France., du Manoir S; INSERM U1194, 34298 Montpellier cedex 5, Montpellier, France. stanislas.dumanoir@inserm.fr.; Institut de Recherche en Cancérologie de Montpellier, Université de Montpellier, 34298 Montpellier cedex 5, Montpellier, France. stanislas.dumanoir@inserm.fr., Tiezzi DG; Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. dtiezzi@usp.br.; CISBi - Center for Integrative Systems Biology - Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. dtiezzi@usp.br.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2017 Jun 06; Vol. 7 (1), pp. 2851. Date of Electronic Publication: 2017 Jun 06.
DOI: 10.1038/s41598-017-02761-6
Abstrakt: 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.
Databáze: MEDLINE
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