Fibronectin rescues estrogen receptor alpha from lysosomal degradation in breast cancer cells.

ROCIO SAMPAYO; TOSCANI ANDRES MARTIN; RUBASHKIN; THI; MASULLO; VIOLI; LATKIN; CASERES; HINES; FEDERICO COLUCCIO LESKOW; STEFANI; CHIALVO; BISSELL; WEAVER VM; MARINA SIMIAN

JOURNAL OF CELL BIOLOGY

ROCKEFELLER UNIV PRESS

Año: 2018

0021-9525

Breast cancer is the leading cause of cancer death in women, worldwide. The adjuvanttherapy of choice for women with estrogen receptor (ER)-positive tumors is endocrinetherapy with tamoxifen (Tam), a selective ER modulator. We previously showed thatfibronectin (FN), one of the most abundant proteins within the extracellular matrix(ECM), induces Tam resistance in breast cancer cells and this effect is mediated by 1-integrin, its main receptor at the cell membrane. The data presented here demonstratea novel association between ER and 1-integrin. This association takes place at theplasma membrane and regulates ER subcellular localization, its degradation rate andboth its genomic and non-genomic activities. Conversely, ER affects 1-integrinactivity by modulating its internalization and recycling dynamics. Interestingly,  17-estradiol induces endocytosis of ER:1-integrin complexes. Some of these vesiclesfollow the lysosomal pathway unless FN is present within the ECM; under theseconditions, the endosomes are recycled to the plasma membrane, inhibitingER and 1-integrin lysosomal degradation.