INVESTIGADORES
JAHN Graciela Alma
congresos y reuniones científicas
Título:
ESTRADIOL PROMOTES CELLULAR ADHESION AND MIGRATION VIA FAK/PAXILLIN/Cdc42/N-WASP/Arp2/3 COMPLEX IN BREAST CANCER CELLS
Autor/es:
SHORTREDE JE; NEIRA FJ; UZAIR ID; JAHN GA; FLAMINI MI; SANCHEZ AM
Lugar:
Estancia Grande
Reunión:
Congreso; XXXII REUNIÓN CIENTÍFICA ANUAL DE LA SOCIEDAD DE BIOLOGÍA DE CUYO; 2014
Institución organizadora:
SOCIEDAD DE BIOLOGÍA DE CUYO
Resumen:
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 actin cytoskeleton key regulators, 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 who is responsible for the branching of actin filaments. We show that 17-estradiol (E2) induces paxillin phosphorylation/activation and its translocation toward membrane sites where focal adhesion complexes are assembled. This process is triggered via a Gi1/G protein dependent signal, and a rapid extra-nuclear signaling of Estrogen Receptor (ER) to c-Src/FAK/paxillin. When paxillin is activated, it recruits the small GTPase cdc42 and this triggers N-WASP phosphorylation. This results in Arp2/3 complex translocation 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 these actions in breast cancer cell motility. Our work intent to clarify estrogen effects on breast cancer metastasis and may provide new targets for therapeutic interventions.