RT Journal Article
SR Electronic
T1 Leptin induces cell migration and invasion in a FAK-Src- dependent manner in breast cancer cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 631143
DO 10.1101/631143
A1 Juan C. Juárez-Cruz
A1 Miriam Daniela Zuñiga-Eulogio
A1 Monserrat Olea-Flores
A1 Eduardo Castañeda-Saucedo
A1 Miguel Ángel Mendoza-Catalán
A1 Carlos Ortuño-Pineda
A1 Ma. Elena Moreno-Godínez
A1 Sócrates Villegas-Comonfort
A1 Teresita Padilla-Benavides
A1 Napoleón Navarro-Tito
YR 2019
UL http://biorxiv.org/content/early/2019/05/08/631143.abstract
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.