Leptin induces partial epithelial-mesenchymal transition in a FAK-ERK dependent pathway in MCF10A mammary non-tumorigenic cells.

Epithelial-mesenchymal transition (EMT) is a biological process involved in different steps of tumor progression and metastasis of breast cancer cells. Epidemiological studies suggest a link between obesity and the progression of breast cancer. Leptin is an adipocyte-secreted hormone which can promote cell migration and invasion as part of EMT in breast cancer cells. We investigated the effect of leptin on expression of EMT markers in MCF10A cells, as well as, the role of FAK and ERK in this process. We found that leptin induces morphological changes from an epithelial phenotype towards a mesenchymal phenotype and promotes cell migration in MCF10A cells. Moreover, leptin induces an increase in vimentin expression, changes in the cellular localization of E-cadherin and increase in FAK and ERK phosphorylation. Furthermore, using FAK and ERK chemical inhibitors we show that leptin regulates EMT markers in a FAK and ERK dependent manner. In conclusion, leptin promotes vimentin expression and cell migration in a FAK and ERK dependent pathway in the non-tumorigenic epithelial cell line MCF10A.