Melatonin attenuates hypoxia-induced epithelial-mesenchymal transition and cell aggressive via Smad7/ CCL20 in glioma

Tumor recurrence in gliomas is partly attributed to increased epithelial–mesenchymal transition (EMT) and enhanced tumor cell dissemination in the adjacent brain parenchyma. Thus, exploring effective strategies for against EMT-like changes in glioma invasion and recurrence will be important for glioma treatment. In this study, we investigated the roles of melatonin in hypoxia-induced EMT suppression, and found that melatonin could significantly suppress the release of the cytokine, CCL20, from cancer cells and antagonize glioma cell metastasis and invasion under hypoxic stress in glioma cells. Furthermore, our findings show that melatonin deregulates Smad7 expression to suppress TGFβ/Smad-mediated increase in CCL20 transcript levels and CCL20-induced EMT occurrence, suggesting a potential anti-EMT therapeutic role for melatonin in malignant transformation in gliomas.