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.