REGULATORY ACTIONS OF LH ON BREAST CANCER CELL MIGRATION AND INVASION VIA KINASE AND SCAFFOLD PROTEINS.

UZAIR ID; MONDACA JM; CASTRO GUIJARRO AC; VANDERHOEVEN F; FLAMINI MI; SANCHEZ AM

PALMA, mollocarca

Workshop; 2nd International Workshop on Translational Cancer Research; 2021

Fundació Institut d'Investigació Sanitària Illes Balears

Background: Breast cancer (BC) is a major public health problem affecting women worldwide. Approximately, 80% of diagnosed cases are hormone-dependent breast cancers (BC). Hormones are known to stimulate tumor development and progression. In this setting, tentative evidence suggests that luteinizing hormone (LH) may also play a role in tumors. In BC cells that express functional LH receptors (LHR), this hormone regulates cell migration and invasion by controlling several kinases that activate actin cytoskeletal proteins. Methodology: We employed T-47D BC cell line and performed treatments with LH and/or chemical inhibitors. After treatments, cells were prepared for western blot, indirect immunofluorescence and immunoprecipitation. Also, cell adhesion, migration and invasion assays were performed. Results: We show that LH induces phosphorylation of paxillin and its translocation toward the plasmatic membrane, where focal adhesion complexes are assembled. This process is triggered via a rapid extra-gonadal LHR signaling to Src/FAK/paxillin, which results in the phosphorylation/activation of the nucleation promoter factors cortactin and N-WASP. As a consequence, Arp2/3 complex induces actin polymerization, essential to promote cell adhesion, migration, and invasion, thus enhancing metastatic spread of cells. Discussion: Our findings provide relevant information about gonadotrophins actions in BC. This information helps us understand the extragonadal effects of LH on BC metastasis. This research may provide new perspectives for therapeutic treatment, especially for women with high serum levels of gonadotrophins, developing new drugs that decrease the circulating amounts of LH, with the potential either to decrease the development of breast cancers or to help controlling cancer progression.