IMBECU   20882
INSTITUTO DE MEDICINA Y BIOLOGIA EXPERIMENTAL DE CUYO
Unidad Ejecutora - UE
artículos
Título:
Retinoic acid induces nuclear FAK translocation and reduces breast cancer cell adhesion through Moesin, FAK, and Paxillin
Autor/es:
SHORTREDE JE; SANCHEZ AM; FLAMINI MI; VARGAS ROIG LM
Revista:
MOLECULAR AND CELLULAR ENDOCRINOLOGY.
Editorial:
ELSEVIER IRELAND LTD
Referencias:
Lugar: Amsterdam; Año: 2016 p. 1 - 11
ISSN:
0303-7207
Resumen:
Breast cancer is the most commonmalignancy in women, with metastases being the cause of death in 98%. Inprevious works we have demonstrated that retinoic acid (RA), the main retinoicacid receptor (RAR) ligand, is involved in the metastatic process by inhibitingmigration through a reduced expression of the specific migration-relatedproteins Moesin, c-Src, and FAK. At present, our hypothesis is that RA alsoacts for short periods in a non-genomic action to cooperate with motilityreduction and morphology of breast cancer cells. Here we identify that theadministration of 10_6 M RA (10e20 min) induces theactivation of the migration-related proteins Moesin, FAK, and Paxillin in T-47Dbreast cancer cells. The phosphorylation exerted by the selective agonists forRARa and RARb, on Moesin, FAK,and Paxillin was comparable to the activation exerted by RA. The RARg agonist only led to a weak activation, suggesting the involvement of RARa and RARb in this pathway. We then treated thecells with different inhibitors that are involved in cell signaling to regulatethe mechanisms of cell motility. RA failed to activate Moesin, FAK, andPaxillin in cells treated with Src inhibitor (PP2) and PI3K inhibitor (WM),suggesting the participation of Src-PI3K in this pathway. Treatment with 10_6 M RA for 20 minsignificantly decreased cell adhesion. However, when cellswere treated with 10_6 M RA and FAK inhibitor, the RA did notsignificantly inhibit adhesion, suggesting a role of FAK inthe adhesion inhibited by RA. By Immunofluorescence and immunoblotting analysiswe demonstrated that RA induced nuclear FAK translocation leading to a reducedcellular adhesion. These findings provide new information on theactions of RA for short periods. RA participates in cell adhesion andsubsequent migration, modulating the relocation and activation of proteinsinvolved in cell migration.