info:eu-repo/semantics/article
Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells
Fecha
2018-08Registro en:
Sampayo, Rocío Guadalupe; Toscani, Andrés Martin; Rubashkin, Matthew G.; Thi, Kate; Masullo, Luciano Andrés; et al.; Fibronectin rescues estrogen receptor α from lysosomal degradation in breast cancer cells; Rockefeller University Press; Journal of Cell Biology; 217; 8; 8-2018; 2777-2798
0021-9525
CONICET Digital
CONICET
Autor
Sampayo, Rocío Guadalupe
Toscani, Andrés Martin
Rubashkin, Matthew G.
Thi, Kate
Masullo, Luciano Andrés
Violi, Ianina Lucila
Lakins, Jonathon N.
Caceres, Alfredo Oscar
Hines, William C.
Coluccio Leskow, Federico
Stefani, Fernando Daniel
Chialvo, Dante Renato
Bissell, Mina J.
Weaver, Valerie M.
Simian, Marina
Resumen
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.