Embryonic transcription factor SOX9 drives breast cancer endocrine resistance

Proceedings of the National Academy of Sciences of the United States of America
Rinath JeselsohnMyles Brown

Abstract

The estrogen receptor (ER) drives the growth of most luminal breast cancers and is the primary target of endocrine therapy. Although ER blockade with drugs such as tamoxifen is very effective, a major clinical limitation is the development of endocrine resistance especially in the setting of metastatic disease. Preclinical and clinical observations suggest that even following the development of endocrine resistance, ER signaling continues to exert a pivotal role in tumor progression in the majority of cases. Through the analysis of the ER cistrome in tamoxifen-resistant breast cancer cells, we have uncovered a role for an RUNX2-ER complex that stimulates the transcription of a set of genes, including most notably the stem cell factor SOX9, that promote proliferation and a metastatic phenotype. We show that up-regulation of SOX9 is sufficient to cause relative endocrine resistance. The gain of SOX9 as an ER-regulated gene associated with tamoxifen resistance was validated in a unique set of clinical samples supporting the need for the development of improved ER antagonists.

References

Feb 1, 1986·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J N IngleD I Twito
Oct 15, 1996·Proceedings of the National Academy of Sciences of the United States of America·B HansteinM Brown
May 3, 2005·Nature Reviews. Cancer·Karen BlythJames C Neil
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Mar 1, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·James N IngleUNKNOWN North Central Cancer Treatment Group Trial N0032
Oct 3, 2006·Nature Genetics·Jason S CarrollMyles Brown
Dec 26, 2006·Nature Cell Biology·Marie-Liesse Asselin-LabatJane E Visvader
Mar 16, 2007·Neoplasia : an International Journal for Oncology Research·Daniel R RhodesArul M Chinnaiyan
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
Sep 27, 2008·Molecular Endocrinology·Susan A KrumMyles Brown
Oct 9, 2008·Bioinformation·Da Wei HuangRichard A Lempicki
Mar 6, 2009·Genome Biology·Ben LangmeadSteven L Salzberg
May 29, 2009·BMC Bioinformatics·Weijun LuoPeter J Woolf
Sep 22, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Angelo Di LeoMiguel Martin
Oct 29, 2010·Genome Biology·Simon Anders, Wolfgang Huber
Feb 24, 2011·Annals of Oncology : Official Journal of the European Society for Medical Oncology·G CuriglianoA Goldhirsch
Sep 13, 2011·World Journal of Surgical Oncology·Amit AgrawalK L Cheung
Oct 26, 2011·Cell Cycle·Kevin A Janes
Mar 6, 2012·Cell·Wenjun GuoRobert A Weinberg
Jun 20, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Linda Sofie LindströmJonas Bergh
Jun 23, 2012·Nature·Matthew J EllisElaine R Mardis
Aug 3, 2012·The New England Journal of Medicine·Rita S MehtaGabriel N Hortobagyi
Sep 1, 2012·Nature Protocols·Jianxing FengXiaole Shirley Liu
Nov 23, 2012·Genome Research·Vasiliki TheodorouJason S Carroll

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Citations

Dec 5, 2017·The Journal of Clinical Investigation·Prachi MishraStefan Ambs
Oct 5, 2017·International Journal of Cancer. Journal International Du Cancer·Lokesh Dalasanur NagaprashanthaSharad S Singhal
Feb 15, 2018·Endocrine-related Cancer·Carolyn M Klinge
Jan 9, 2019·Journal of Molecular Endocrinology·Shu-Ching M WangGeorge E O Muscat
Mar 2, 2019·Cerebral Cortex·Carmen FalconeAntonello Mallamaci
Dec 18, 2018·Endocrine-related Cancer·KeeMing ChiaElgene Lim
Apr 11, 2019·PloS One·Silvia-E GlontRasmus Siersbaek
Jan 3, 2020·PLoS Genetics·Catherine L PigginChristopher J Ormandy
Sep 10, 2019·Frontiers in Endocrinology·Md Moquitul Haque, Kartiki V Desai
Oct 19, 2019·Cancer Cell International·Yue Yu, Xu-Chen Cao
Jan 20, 2019·Journal of Experimental & Clinical Cancer Research : CR·Yue YuXu-Chen Cao
May 10, 2019·Journal of Mammary Gland Biology and Neoplasia·Gaurav A MehtaMichael L Gatza
Dec 13, 2019·Proceedings of the National Academy of Sciences of the United States of America·Xiaoyong FuRachel Schiff
May 19, 2020·BioMed Research International·Xiulei ZhangGuangzhi Liu
Feb 4, 2019·Breast Cancer Research and Treatment·Elena StrekalovaVincent L Cryns
Dec 20, 2018·Communications Biology·Naoko KogataBeatrice A Howard
Jun 11, 2019·Frontiers in Endocrinology·Aradhana RaniJohn Murphy
Jan 11, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mannan NouriRalph Buttyan
Sep 13, 2018·Molecular Cancer Research : MCR·Yue XueQingqing Wang
Aug 30, 2020·Cancer Research·Eugen DhimoleaConstantine S Mitsiades
Jul 15, 2020·Molecular Cancer Research : MCR·Yanxia MaPowel H Brown
Apr 15, 2020·Cancer Cell·Ariella B HankerCarlos L Arteaga
Dec 29, 2020·Frontiers in Pharmacology·Jingwei YaoJianhong Zuo
Feb 16, 2021·Seminars in Cell & Developmental Biology·Yu Liu, Wenjun Guo
Feb 2, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Munmun PandaBijesh K Biswal
Jan 9, 2020·Biochemical Pharmacology·Samir JanaSharad S Singhal
Jan 12, 2020·Communications Biology·Naoko KogataBeatrice A Howard
Aug 8, 2021·International Journal of Molecular Sciences·Gink N YangAllison J Cowin
Oct 9, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ozge SaatciOzgur Sahin
Oct 16, 2021·Journal of Cellular and Molecular Medicine·Yuan LiYen-Hua Huang
Sep 18, 2021·Cancer Research·Narendra Wajapeyee, Romi Gupta

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