Overexpression of ALK4 inhibits cell proliferation and migration through the inactivation of JAK/STAT3 signaling pathway in glioma

Aristaless-like homeobox 4 (ALK4) is a member of ALK proteins family and plays an important role in tumorigenesis. However, the expression and function of ALK4 in glioma remain largely unknown. The aim of our study was to elucidate its expression pattern in human glioma tissues and cell lines, as well as its functions in glioma cells. Our results demonstrated that ALK4 was lowly expressed in human glioma tissues and cell lines. Additionally, overexpression of ALK4 significantly suppressed the proliferation, migration and invasion of glioma cells, as well as inhibited the epithelial-mesenchymal transition (EMT) phenotype in glioma cells. Furthermore, overexpression of ALK4 significantly downregulated the phosphorylation levels of JAK2 and STAT3 in U87 cells. STAT3 inhibitor (Niclosamide) obviously enhanced ALK4-inhibted glioma cell proliferation and invasion. In conclusion, we demonstrated that overexpression of ALK4 suppressed glioma cell proliferation, migration and invasion through the inactivation of JAK/STAT3 signaling pathway. Thus, ALK4 may be a potential therapeutic target for the treatment of glioma.