Estradiol promotes the cellular adhesion and migration via FAK/PAXILLIN/CDC42/N-WASP/ARP2/3 complex in breast cancer cells

SHORTREDE JE; NEIRA FJ; UZAIR ID; JAHN GA; FLAMINI MI; SANCHEZ AM

Congreso; Sociedad de Biología de Cuyo.; 2014

Breast cancer (BC) is the most common neoplasm affecting women. Cellular migration is a crucial step for cancer cells to invade nearby tissue. This actions are conducted by many key regulators of actin cytoskeleton, like paxillin and N-WASP, where they link extracellular stimuli to actin reorganization. N-WASP acts as a scaffolding protein that relays signals from small GTPases to the Arp2/3 complex that is responsible for the branching of actin filaments. We show that 17ß-estradiol (E2) induces phosphorylation/activation of paxillin and its translocation toward membrane sites where focal adhesion complexes are assembled. This process is triggered via a Gai1/Gß protein-dependent, rapid extra-nuclear signaling of estrogen receptor α (ERa) signal to c-Src/FAK/paxillin. When paxillin is activated, recruits the small GTPase cdc42 and this triggers 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 FAK/paxillin and N-WASP is necessary for cell migration and adhesion induced by E2 in breast cancer cells. Our findings provide a molecular mechanism by which estrogens exert this action in breast cancer cells motility. This information helps to understand the effects of estrogen on breast cancer metastasis and may provide new targets for therapeutic interventions.