LH CONTROLS BREAST CANCER CELLS ADHESION, MIGRATION AND INVASION MEDIATES FAK/PAXILLIN/CORTACTIN AND N-WASP.

MONDACA JM; FLAMINI MI; SANCHEZ AM

Mendoza

Congreso; XXXIV Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2016

Reproductive hormones influence breast cancer development and progression. While the actions of sex steroids inthis setting are established, tentative evidence suggests that luteinizing hormone (LH) may also play a role, yet thisremains elusive. We identify that T-47D breast cancer cells express functional receptors for LH (LHR), and that thishormone regulate breast cancer cell motility and invasion through the control of the actin cytoskeleton proteins. Weshow that LH induces phosphorylation/activation of Paxillin and its translocation toward membrane sites where focaladhesion complexes are assembled. This process is triggered via a rapid extra-gonadal signaling of LHR signal to cSrc/FAK/paxillin/Cortactin.When paxillin is activated, recruits the small GTPase cdc42 and this triggers Cortactinand N-WASP phosphorylation. This result in the translocation of Arp2/3 complexes at sites where membranestructures related to cell movement are formed. Recruitment of Src/FAK/Paxillin/Cortactin and N-WASP isnecessary for cell adhesion, migration and invasion induced by LH in breast cancer cells. Our findings provide amolecular mechanism by which gonadotropins exert this action in breast cancer cells motility. This information helpsto understand the extragonadal effects of LH on breast cancer metastasis and may provide new targets for therapeuticinterventions.