LH CONTROLS BREAST CANCER CELL MIGRATION AND INVASION VIA PAXILLIN/CORTACTIN/N-WASP.

CONTE GRAND J; MONDACA JM; FLAMINI MI; SANCHEZ AM

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2018

Reproductive hormones influence breast cancer development and progression. While the actions of sex steroids in this setting are established, tentative evidence suggests that luteinizing hormone (LH) may also play a role, yet this remains elusive. We identify that T-47D breast cancer cells express functional receptor for LH, and this hormone regulate breast cancer cell motility and invasion. This occurs through the control of the actin cytoskeleton and the formation of cortical actin aggregates and focal adhesion complexes. Such actions are mediated by the cytoskeletal controllers like Paxillin, Cortactin and N-WASP. N-WASP phosphorylation is found to be triggered by a rapid extragonadal signaling of LH receptor (LHR) to c-Src, Focal Adhesion kinase (FAK) and Paxillin. After N-WASP phosphorylation by LH, the Arp-2/3 complex concentrates at actin nucleation sites, where it triggers the local reorganization of actin fibers, promoting the breast cancer cell movement. These results contribute to the emerging area of investigation on the extra-gonadal actions of gonadotrophins suggesting potential implications of the changing levels of these hormones throughout life for the development or progression of breast cancer. Plus, they may have clinical implications for the use of drugs that modulate gonadotrophins in breast cancer patients.