Through its varied effects on multiple cell types in the tumor microenvironment including fibroblasts, immune cells, and vascular cells, Dkk-3 appears to have the ability to enhance or reduce cancer progression by altering tumor cell responses to signals mediated by Wnts (β-catenin-dependent and -independent via JNK), TGF-β, and Hh. The gene discussed is MAPK8; the disease is cancer.