Department of Biochemistry and Molecular Pharmacology
Amino Acids, Peptides, and Proteins | Cancer Biology | Cells | Enzymes and Coenzymes | Neoplasms
Breast cancer is the most common invasive neoplasia, and the second leading cause of the cancer deaths in women worldwide. Mammary tumorigenesis is severely linked to obesity, one 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, metalloprotease secretion, and invasion. We found that leptin activates FAK and Src, and induces the localization of FAK to the focal adhesions. Interestingly, leptin promotes the activation of FAK through a Src and STAT3-dependent canonical pathway. Specific inhibitors of FAK, Src and STAT3 showed that the effect exerted by leptin in cell migration in breast cancer cells is dependent on these proteins. Moreover, we established that leptin promotes the secretion of the extracellular matrix remodelers, MMP-2 and MMP-9 and invasion 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.
Leptin, FAK, Src, cell migration, metalloproteases, invasion, breast cancer
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Copyright: © 2019 The authors. Creative Commons Attribution 4.0 International (CC BY 4.0)
DOI of Published Version
Endocr Connect. 2019 Oct 1. pii: EC-19-0442. doi: 10.1530/EC-19-0442. [Epub ahead of print] Link to article on publisher's site
Juarez-Cruz JC, Zuniga-Eulogio MD, Olea-Flores M, Castaneda-Saucedo E, Mendoza-Catalan MA, Ortuno-Pineda C, Moreno-Godinez ME, Villegas-Comonfort S, Padilla-Benavides T, Navarro-Tito N. (2019). Leptin induces cell migration and invasion in a FAK-Src- dependent manner in breast cancer cells. Open Access Articles. https://doi.org/10.1530/EC-19-0442. Retrieved from https://escholarship.umassmed.edu/oapubs/4009
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This work is licensed under a Creative Commons Attribution 4.0 License.