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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.

Titel:	Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype.
Autor/in / Beteiligte Person:	da Silveira WA ; Palma, PVB ; Sicchieri, RD ; Villacis, RAR ; Mandarano, LRM ; Oliveira, TMG ; Antonio, HMR ; Andrade, JM ; Muglia, VF ; Rogatto, SR ; Theillet, C ; du Manoir S ; Tiezzi, DG
Link:	Zum Volltext
Zeitschrift:	Scientific reports, Jg. 7 (2017-06-06), Heft 1, S. 2851
Veröffentlichung:	London : Nature Publishing Group, copyright 2011-, 2017
Medientyp:	academicJournal
ISSN:	2045-2322 (electronic)
DOI:	10.1038/s41598-017-02761-6
Schlagwort:	Animals Biomarkers Breast Neoplasms genetics Breast Neoplasms pathology Disease Models, Animal Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Heterografts Humans Mice Neoplastic Stem Cells pathology Phenotype Protein Binding Signal Transduction Transcriptome Breast Neoplasms immunology Breast Neoplasms metabolism Neoplastic Stem Cells immunology Neoplastic Stem Cells metabolism Transcription Factors metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Sci Rep] 2017 Jun 06; Vol. 7 (1), pp. 2851. <i>Date of Electronic Publication: </i>2017 Jun 06. MeSH Terms: Breast Neoplasms / immunology ; Breast Neoplasms / metabolism ; Neoplastic Stem Cells / immunology ; Neoplastic Stem Cells / metabolism ; Transcription Factors / *metabolism ; Animals ; Biomarkers ; Breast Neoplasms / genetics ; Breast Neoplasms / pathology ; Disease Models, Animal ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Heterografts ; Humans ; Mice ; Neoplastic Stem Cells / pathology ; Phenotype ; Protein Binding ; Signal Transduction ; Transcriptome References: Nat Rev Cancer. 2013 Feb;13(2):97-110. (PMID: 23344542) ; Mol Oncol. 2014 Mar;8(2):431-43. (PMID: 24394560) ; J Leukoc Biol. 2002 Feb;71(2):173-83. (PMID: 11818437) ; Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. (PMID: 16199517) ; Cell Cycle. 2004 Apr;3(4):396-400. (PMID: 14752272) ; Cancer Sci. 2012 May;103(5):913-20. (PMID: 22320227) ; Lab Invest. 2008 May;88(5):459-63. (PMID: 18379567) ; Lab Invest. 2013 Sep;93(9):970-82. (PMID: 23917877) ; Virchows Arch. 2012 Jun;460(6):545-53. (PMID: 22562130) ; Am J Gastroenterol. 2010 Jan;105(1):125-31. (PMID: 19861957) ; Med Oncol. 2012 Sep;29(3):1479-85. (PMID: 21713550) ; Front Biosci (Landmark Ed). 2009 Jan 01;14 :475-85. (PMID: 19273079) ; J Biomed Inform. 2011 Feb;44(1):48-58. (PMID: 20460173) ; Semin Cancer Biol. 2004 Jun;14(3):195-200. (PMID: 15246055) ; Med Oncol. 2012 Jun;29(2):448-53. (PMID: 21347717) ; Mod Pathol. 2010 May;23 Suppl 2:S60-4. (PMID: 20436504) ; Int J Cancer. 2009 Feb 15;124(4):853-61. (PMID: 19035451) ; BMC Cancer. 2010 Nov 04;10:604. (PMID: 21050467) ; J Immunol. 2015 May 15;194(10 ):4650-6. (PMID: 25862820) ; PLoS One. 2011;6(6):e20636. (PMID: 21695188) ; J Leukoc Biol. 2001 Apr;69(4):531-7. (PMID: 11310838) ; Stem Cells. 2016 Aug;34(8):1997-2007. (PMID: 27251010) ; Int J Biochem Cell Biol. 2010 Jan;42(1):21-4. (PMID: 19782763) ; Immunol Cell Biol. 2003 Jun;81(3):171-5. (PMID: 12752680) ; Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8418-23. (PMID: 12829800) ; Cell. 2011 Mar 4;144(5):646-74. (PMID: 21376230) ; Mol Cancer. 2015 Aug 07;14:149. (PMID: 26245467) ; J Immunol. 2004 Sep 15;173(6):3755-62. (PMID: 15356122) ; Oncoscience. 2015 Aug 31;2(10):841-2. (PMID: 26682272) ; Nat Rev Genet. 2009 Apr;10 (4):252-63. (PMID: 19274049) ; Nat Med. 2011 Oct 23;17(11):1514-20. (PMID: 22019887) ; Oncogene. 2012 Mar 1;31(9):1196-206. (PMID: 21785460) ; Cell. 2013 Jul 3;154(1):61-74. (PMID: 23827675) ; Proc Natl Acad Sci U S A. 2011 May 10;108(19):7950-5. (PMID: 21498687) ; Nat Immunol. 2013 Oct;14(10):1014-22. (PMID: 24048123) ; Sci Rep. 2015 Nov 04;5:16066. (PMID: 26530441) ; CA Cancer J Clin. 2015 Mar;65(2):87-108. (PMID: 25651787) ; Cancer Res. 2013 Dec 15;73(24):7290-300. (PMID: 24142344) ; Methods Mol Biol. 2015;1293:1-49. (PMID: 26040679) ; Innate Immun. 2016 Apr;22(3):238-44. (PMID: 26888964) ; Science. 2008 Feb 15;319(5865):921-6. (PMID: 18187620) ; Eur J Immunol. 2001 Aug;31(8):2521-7. (PMID: 11500837) ; Mol Immunol. 2011 May;48(9-10):1272-8. (PMID: 21477865) ; Neuro Oncol. 2010 Oct;12(10):1024-33. (PMID: 20627895) ; Sci Rep. 2015 Jun 30;5:11766. (PMID: 26123483) ; Oncogene. 2008 Oct 6;27(45):5932-43. (PMID: 18836474) ; Oncogene. 2008 Oct 20;27(48):6299-312. (PMID: 18931695) ; Cancer Cell. 2012 Dec 11;22(6):709-24. (PMID: 23201163) ; Blood. 1997 Nov 15;90(10):4099-105. (PMID: 9354680) ; Nature. 2010 Jan 21;463(7279):318-25. (PMID: 20032975) ; Leukemia. 2014 May;28(5):1155-8. (PMID: 24365790) ; BMC Bioinformatics. 2006 Mar 20;7 Suppl 1:S7. (PMID: 16723010) ; Cancer Res. 2009 Feb 15;69(4):1302-13. (PMID: 19190339) ; Development. 2009 Nov;136(21):3531-42. (PMID: 19820181) ; Breast Cancer Res Treat. 2010 Oct;123(3):725-31. (PMID: 20020197) ; Int Immunol. 2012 Sep;24(9):539-50. (PMID: 22914861) ; Stem Cell Reports. 2013 Dec 27;2(1):78-91. (PMID: 24511467) Substance Nomenclature: 0 (Biomarkers) ; 0 (Transcription Factors) Entry Date(s): Date Created: 20170608 Date Completed: 20181218 Latest Revision: 20181218 Update Code: 20231215 PubMed Central ID: PMC5460106

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