Skip to main content
eScholarship
Open Access Publications from the University of California

Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells

  • Author(s): Sampayo, RG
  • Toscani, AM
  • Rubashkin, MG
  • Thi, K
  • Masullo, LA
  • Violi, IL
  • Lakins, JN
  • Cáceres, A
  • Hines, WC
  • Leskow, FC
  • Stefani, FD
  • Chialvo, DR
  • Bissell, MJ
  • Weaver, VM
  • Simian, M
  • et al.
Abstract

© 2018 Sampayo et al. 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.

Many UC-authored scholarly publications are freely available on this site because of the UC Academic Senate's Open Access Policy. Let us know how this access is important for you.

Main Content
Current View