LH controls breast cancer cells adhesion, migration and invasion mediates FAK/Paxillin/Cortactin and N-WASP

MONDACA JOSELINA MAGALI; FLAMINI MARINA INES; SANCHEZ ANGEL MATIAS

Mendoza

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

Sociedad de Biología de Cuyo

LH CONTROLS BREAST CANCER CELLS ADHESION, MIGRATION AND INVASION MEDIATES FAK/PAXILLIN/CORTACTIN AND N-WASP. Mondaca JM, Flamini MI and Sanchez AM*. Laboratorio de Transduccion de Señales y Movimiento Celular, IMBECU-CCT-CONICET-Mendoza. (*) amsanchez@mendoza-conicet.gob.arReproductive 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 receptors for LH (LHR), and that this hormone regulate breast cancer cell motility and invasion through the control of the actin cytoskeleton proteins. We show that LH induces phosphorylation/activation of Paxillin and its translocation toward membrane sites where focal adhesion complexes are assembled. This process is triggered via a rapid extra-gonadal signaling of LHR signal to c-Src/FAK/paxillin/Cortactin. When paxillin is activated, recruits the small GTPase cdc42 and this triggers Cortactin and N-WASP phosphorylation. This results in the translocation of Arp2/3 complexes at sites where membrane structures related to cell movement are formed. Recruitment of Src/FAK/Paxillin/Cortactin and N-WASP is necessary for cell adhesion, migration and invasion induced by LH in breast cancer cells. Our findings provide a molecular mechanism by which gonadotropins exert this action in breast cancer cells motility. This information helps to understand the extragonadal effects of LH on breast cancer metastasis and may provide new targets for therapeutic interventions.Área temática: Biología General, Celular y Molecular (BM), Mendoza