PT - JOURNAL ARTICLE AU - Juárez-Cruz, Juan C. AU - Zuñiga-Eulogio, Miriam Daniela AU - Olea-Flores, Monserrat AU - Castañeda-Saucedo, Eduardo AU - Mendoza-Catalán, Miguel Ángel AU - Ortuño-Pineda, Carlos AU - Moreno-Godínez, Ma. Elena AU - Villegas-Comonfort, Sócrates AU - Padilla-Benavides, Teresita AU - Navarro-Tito, Napoleón TI - Leptin induces cell migration and invasion in a FAK-Src- dependent manner in breast cancer cells AID - 10.1101/631143 DP - 2019 Jan 01 TA - bioRxiv PG - 631143 4099 - http://biorxiv.org/content/early/2019/05/08/631143.short 4100 - http://biorxiv.org/content/early/2019/05/08/631143.full AB - Breast cancer is the most common invasive neoplasia, and the second leading cause of death associated with cancer in women worldwide. Mammary tumorigenesis is severely linked to obesity, the potential connection is leptin. Leptin is a hormone secreted by adipocytes, which contributes to the progression of breast cancer. Cell migration, metalloproteases secretion, and invasion are cellular processes associated with various stages of metastasis. These processes are regulated by the kinases FAK and Src. In this study, we utilized the breast cancer cell lines MCF7 and MDA-MB-231 to determine the effect of leptin on FAK and Src kinases activation, cell migration, metalloproteases secretion, and invasion. By Western blot we found that leptin activates FAK and Src, and induces the localization of FAK to the focal adhesions. Specific inhibitors of FAK and Src showed that the effect exerted by leptin in cell migration, and invasion in breast cancer cells is dependent on these kinases. Moreover, by gelatin zymmography we established that leptin promotes the secretion of the extracellular matrix remodelers, MMP-2 and MMP-9, in a FAK and Src dependent manner. Our findings strongly suggest that leptin promotes the development of a more aggressive invasive phenotype in mammary cancer cells.