Leptin enhances migration of human papillary thyroid cancer cells through the PI3K/AKT and MEK/ERK signaling pathways

The incidence of thyroid cancer has remarkably increased in recent years. Epiden-hologic data suggest that obesity is associated with an increased incidence of several types of malignancies, including thyroid cancer. Leptin, an adipocyte-derived cytokine, has been shown to be involved in cancer development and progression. We previously demonstrated that papillary thyroid cancer expressing leptin receptor and/or leptin has a higher incidence of lymph node metastasis. In this study, we investigated the effects of leptin on cell migration in K1 and B-CPAP papillary thyroid cancer cells. Expression of leptin receptor was observed in both cell lines. Leptin enhanced the migratory activity significantly in a dose-dependent manner. We showed that leptin induced AKT and extracellular signal-regulated kinase (ERK) phosphorylation. Inhibition of phosphatidylinositol 3-kinase and ERK activation using pharmacological inhibitors effectively blocked leptin-induced migration of K1 and B-CPAP cells. Taken together, this study provides new mechanistic evidence for a role of leptin in the regulation of papillary thyroid cancer progression by stimulating tumor cell migration.