Molecular basis of LH action on breast cancer cell migration and invasion via kinase and scaffold proteins.

UZAIR, ID; MONDACA, JM; CASTRO GUIJARRO, AC; VANDERHOEVEN, F; FERNANDEZ-MUÑOZ, JM; REDONDO, A; SANCHEZ, AM; FLAMINI, MI

Palma

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

Background and Aims:Breast cancer (BC) is a major public health problem affecting women worldwide. Approximately, 80% ofdiagnosed cases are hormone-dependent breast cancers (BC). Hormones are known to stimulate tumordevelopment 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 hormoneregulates cell migration and invasion by controlling several kinases that activate actin cytoskeletalproteins.Methods:We employed T-47D BC cell line and performed treatments with LH and/or chemical inhibitors. Aftertreatments, cells were prepared for western blot, indirect immunofluorescence andimmunoprecipitation. Also, cell adhesion, migration and invasion assays were performed.Results:We show that LH induces phosphorylation of paxillin and its translocation toward the plasmaticmembrane, where focal adhesion complexes are assembled. This process is triggered via a rapid extragonadalLHR signaling to Src/FAK/paxillin, which results in the phosphorylation/activation of thenucleation promoter factors cortactin and N-WASP. As a consequence, Arp2/3 complex induces actinpolymerization, essential to promote cell adhesion, migration, and invasion, thus enhancing metastaticspread of cells.Conclusions:Our findings provide relevant information about gonadotrophins actions in BC. This information helps usunderstand the extragonadal effects of LH on BC metastasis. It may provide new perspectives fortherapeutic treatment, especially for women with high serum levels of gonadotrophins.