Nodal signaling modulates the expression of Oct-4 via nuclear translocation of β-catenin in lung and prostate cancer cells.

Abstract Nodal is a member of transforming growth factor beta (TGF-β) superfamily. Nodal promotes the self-renewal of human cancer stem cells (CSCs) and triggers carcinogenesis of human cancers via an autocrine manner through Smad2/3 pathway. In our study, generation of Nodal-overexpressed cancer cells was constructed, and the effect of Nodal on the stem cell marker Oct-4 was evaluated by overexpression or blocked Nodal/ALKs signaling pathway in non-small cell lung cancer cells A549 and prostate cancer cells PC3. Functionally, Nodal also increased the proliferation via the β-catenin nuclear translocation. This increase was attributed to GSK-3β dephosphorylating, and activin receptor-like kinase 4/7 (ALK4/7) played a major role in human cancer cells. Our study provides a positive understanding of Nodal function in cancer cells and suggests a potential novel target for clinical therapeutic research.