Melanoma-associated antigen family protein-D1 regulation of tumor cell migration, adhesion to endothelium, and actin structures reorganization in response to hypoxic stress.

Melanoma-associated antigen family protein-D1 (MAGE-D1) is a recently identified p75 neurotrophin receptor intracellular binding protein and functions as an adaptor that mediates multiple signaling pathways, including Dlx/Msx-mediated transcription. Here, a new regulatory function for MAGE-D1 in tumor cell motility and adhesion to endothelium is described. MAGE-D1 over-expression suppressed HeLa cell and BEL7402 cell migration, invasion, and adhesion to the monolayer of ECV304 cells. We also report that MAGE-D1 over-expression disrupted actin cytoskeleton rearrangement induced by hypoxia and down-regulated hypoxia inducible factor 1-dependent luciferase gene expression. These findings provide new insight into the ability of MAGE-D1 to suppress the motility and adhesion response of tumor cells by interfering with actin cytoskeleton reorganization and hypoxia inducible factor 1-dependent gene expression.