Endogenous Nodal promotes melanoma undergoing epithelial-mesenchymal transition via Snail and Slug in vitro and in vivo

摘要: Nodal, an important embryonic morphogen, has been reported to modulate tumorigenesis. Epithelial-mesenchymal transition (EMT) plays role in cancer metastasis. We have previously that recombinant Nodal treatment can promote melanoma undergoing EMT, but the effects of endogenous on EMT are still unknown. Here we generated both Nodal-overexpression and -knockdown stable cell lines investigate vitro vivo characteristics Nodal-induced murine cells. cells displayed increased migration ability, accompanied by typical phenotype changes EMT. In contrast, Nodal-knockdown repressed as well reduced motility. Results animal experiments confirmed overexpression metastasis tumor vivo. Mechanistically, found expression Snail Slug involves its activation ALK/Smads PI3k/AKT pathways, which is process However, also was not completely inhibited blocking paracrine activity line suggesting presence additional mechanism(s) This study provides a better understanding function melanoma, suggests targeting potential strategy for therapey.