Wnt/β-catenin up-regulates Midkine expression in glioma cells.

Midkine, also known as neurite growth-promoting factor 2 (NEGF2), plays an important role in cell proliferation, apoptosis and differentiation. Recent studies have shown that Midkine is up-regulated in several types of human cancers. However, the molecular mechanism for its up-regulation remains poorly understood. Activation of Wnt/β-catenin signaling is viewed as crucial for multiple tumor growth and metastasis, including glioma. In the present study, we found that Wnt3a administration or transfection of a constitutively activated β-catenin promoted Midkine expression in glioma cells. We further identified a TCF/LEF binding site, with which beta-catenin interacts, on the proximal promoter region of Midkine gene, by luciferase reporter and chromatin immunoprecipitation assays. Thus, our results suggest a previously unknown Wnt/β-catenin/Midkine molecular network controlling glioma development.