Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells
Abstract
Estrogen receptor α (ERα) is expressed in tissues as diverse as brains and mammary glands. In breast cancer, ERα is a key regulator of tumor progression. Therefore, understanding what activates ERα is critical for cancer treatment in particular and cell biology in general. Using biochemical approaches and superresolution microscopy, we show that estrogen drives membrane ERα into endosomes in breast cancer cells and that its fate is determined by the presence of fibronectin (FN) in the extracellular matrix; it is trafficked to lysosomes in the absence of FN and avoids the lysosomal compartment in its presence. In this context, FN prolongs ERα half-life and strengthens its transcriptional activity. We show that ERα is associated with β1-integrin at the membrane, and this integrin follows the same endocytosis and subcellular trafficking pathway triggered by estrogen. Moreover, ERα+ vesicles are present within human breast tissues, and colocalization with β1-integrin is detected primarily in tumors. Our work unravels a key, clinically relevant mechanism of microenvironmental regulation of ERα signaling.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 06, 2018
- Source ID
- 10.1083/jcb.201703037
Entities
People
- Alfredo Cáceres
- Andrés M. Toscani
- Dante R Chialvo
- Federico Coluccio Leskow
- Fernando D. Stefani
- Ianina L. Violi
- Jonathon N. Lakins
- Kate Thi
- Luciano A Masullo
- Marina Simian
- Matthew G Rubashkin
- Mina Bissell
- Rocío G. Sampayo
- Valerie M Weaver
- William C Hines
Organizations
- Agencia Nacional de Promoción Científica y Tecnológica
- Bunge & Born Foundation
- Fulbright Association
- Fundacion Florencio Fiorini
- Instituto Nacional del Cáncer
- Lawrence Berkeley National Laboratory
- Ministry of Health of Argentina
- National Cancer Institute
- National Institutes of Health
- National Scientific and Technical Research Council
- National University of General San Martín
- Susan G. Komen for the Cure
- The Breast Cancer Research Foundation
- United States Department of Defense
- University of Buenos Aires
- University of California, San Francisco