LH controls breast cancer cell migration and invasion via Paxillin/Cortactin/N-WASP.

FLAMINI MARINA INES; CONTE GRAND JEREMIAS; MONDACA JOSELINA MAGALI; SANCHEZ ANGEL MATIAS

Mar del Plata

Congreso; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2017

Sociedad Argentina de Investigación Clínica (SAIC)

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 here identify that T-47D breast cancer cells express functional receptor for LH, and that this hormone regulates breast cancer cell motility and invasion 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 Paxillin, Cortactin and N-WASP. N-WASP phosphorylation is found to be triggered by a rapid extragonadal signaling of LH receptor (LHR)ˇto c-Src, Focal Adhesion kinase (FAK) and Paxillin. Paxillin recruits the protein kinase Cortactin that directly phosphorylates N-WASP. After N-WASP phosphorylation by LH, the Arp-2/3 complex concentrates at sites of 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.