FOXA1 overexpression mediates endocrine resistance by altering the ER transcriptome and IL-8 expression in ER-positive breast cancer
Abstract
One of the mechanisms of endocrine resistance in estrogen receptor α (ER)-positive (+) breast cancer is the cross-talk between the ER and growth factor receptor pathways leading to altered ER activity and a reprogrammed ER-dependent transcriptome. However, key mediators of this ER-dependent transcriptional reprogramming remain elusive. Here we demonstrate that forkhead box protein A1 (FOXA1) up-regulation via gene amplification or overexpression contributes to endocrine resistance and increased invasiveness phenotypes by altering the ER-dependent transcriptome. We further show that IL-8, one of the top altered FOXA1/ER effectors, plays a key role in mediating these phenotypes and is a potential target to treat ER+/FOXA1-high breast cancer. Our findings provoke a new interplay of FOXA1 in the ER transcriptional program in endocrine-resistant breast cancer.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 06, 2016
- Source ID
- 10.1073/pnas.1612835113
Entities
People
- Agostina Nardone
- Anna Tsimelzon
- C. Kent Osborne
- Carmine De Angelis
- Carolina Gutierrez
- Catherine S. Grasso
- Chad J Creighton
- Dean P. Edwards
- Dolores Lopez-terrada
- Emporia F. Hollingsworth
- Fugen Li
- Joe W. Gray
- Laura M Heiser
- Martin Shea
- Meghana V Trivedi
- Mothaffar F Rimawi
- Myles A. Brown
- Nicholas Wang
- Obi Griffith
- Paul Spellman
- Pavana Anur
- Rachel Schiff
- Resel Pereira
- Rinath Jeselsohn
- Shixia Huang
- Susan Hilsenbeck
- Xiaoyong Fu
Organizations
- American Association for Cancer Research
- Baylor College of Medicine
- Congressionally Directed Medical Research Programs
- Harvard Medical School
- National Cancer Institute
- Oregon Health & Science University
- Susan G. Komen for the Cure
- The Breast Cancer Research Foundation
- University of Houston
- Washington University in St. Louis