دورية أكاديمية

The Lineage Determining Factor GRHL2 Collaborates with FOXA1 to Establish a Targetable Pathway in Endocrine Therapy-Resistant Breast Cancer

التفاصيل البيبلوغرافية
العنوان: The Lineage Determining Factor GRHL2 Collaborates with FOXA1 to Establish a Targetable Pathway in Endocrine Therapy-Resistant Breast Cancer
المؤلفون: Kimberly J. Cocce, Jeff S. Jasper, Taylor K. Desautels, Logan Everett, Suzanne Wardell, Thomas Westerling, Robert Baldi, Tricia M. Wright, Kendall Tavares, Alex Yllanes, Yeeun Bae, Jeremy T. Blitzer, Craig Logsdon, Daniel P. Rakiec, David A. Ruddy, Tiancong Jiang, Gloria Broadwater, Terry Hyslop, Allison Hall, Muriel Laine, Linda Phung, Geoffrey L. Greene, Lesley-Ann Martin, Sunil Pancholi, Mitch Dowsett, Simone Detre, Jeffrey R. Marks, Gregory E. Crawford, Myles Brown, John D. Norris, Ching-yi Chang, Donald P. McDonnell
المصدر: Cell Reports, Vol 29, Iss 4, Pp 889-903.e10 (2019)
بيانات النشر: Elsevier, 2019.
سنة النشر: 2019
المجموعة: LCC:Biology (General)
مصطلحات موضوعية: Biology (General), QH301-705.5
الوصف: Summary: Notwithstanding the positive clinical impact of endocrine therapies in estrogen receptor-alpha (ERα)-positive breast cancer, de novo and acquired resistance limits the therapeutic lifespan of existing drugs. Taking the position that resistance is nearly inevitable, we undertook a study to identify and exploit targetable vulnerabilities that were manifest in endocrine therapy-resistant disease. Using cellular and mouse models of endocrine therapy-sensitive and endocrine therapy-resistant breast cancer, together with contemporary discovery platforms, we identified a targetable pathway that is composed of the transcription factors FOXA1 and GRHL2, a coregulated target gene, the membrane receptor LYPD3, and the LYPD3 ligand, AGR2. Inhibition of the activity of this pathway using blocking antibodies directed against LYPD3 or AGR2 inhibits the growth of endocrine therapy-resistant tumors in mice, providing the rationale for near-term clinical development of humanized antibodies directed against these proteins. : Cocce et al. show that FOXA1 contributes to disease pathogenesis by cooperating with GRHL2 in endocrine therapy-resistant breast cancer. LYPD3 is identified as an actionable downstream target of FOXA1/GRHL2, and humanized antibodies against LYDP3, or its ligand AGR2, demonstrate anti-tumor efficacy in animal models of endocrine therapy-resistant breast tumors. Keywords: FOXA1, tamoxifen, breast cancer, GRHL2, cistrome, enhancer, histone, chromatin, LYPD3
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2211-1247
Relation: http://www.sciencedirect.com/science/article/pii/S2211124719312203; https://doaj.org/toc/2211-1247
DOI: 10.1016/j.celrep.2019.09.032
URL الوصول: https://doaj.org/article/c0b467352d604bac96892990f6f1dd91
رقم الأكسشن: edsdoj.0b467352d604bac96892990f6f1dd91
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:22111247
DOI:10.1016/j.celrep.2019.09.032