TI - Importance of Wnt signaling in the tumor stroma microenvironment . AB - Wnt signaling plays an important role in cancer . Signaling is initiated by binding of Wnt ligands to Frizzled cell surface receptors and results in signaling via one of three pathways , the canonical Wnt pathway , which is the best characterized in both normal tissues and in cancer , and two non-canonical Wnt pathways , the Ca(2+) -dependent and the PCP pathways . Canonical Wnt signaling results in beta-catenin accumulation in the cytoplasm , translocation into the nucleus and activation of transcription of Wnt target genes including the c-Myc oncogene . Some cancer types , including colorectal cancer , have mutations in APC and Axin , which are involved in beta-catenin phosphorylation , such that the canonical pathway is constitutively active . Few studies have investigated the role non-canonical Wnt signaling in cancer , or of Wnt signaling on tumor stromal cells . Wnt overexpression is observed in tumor stroma , as is overexpression of the Wnt pathway inhibitors , secreted Frizzled-related proteins and Dickkopf proteins . Interactions between epithelial cells and stromal cells have been observed to activate Wnt signaling in both cell types . Wnt signaling is also observed in tumor blood vessels and is likely to be activated by signals from tumor cells . Current cancer therapies focus on interfering with canonical Wnt signaling in the tumor cells . Future therapeutic targets for interfering with Wnt signaling include cell surface receptors such as the RYK and Ror2 receptors and secreted signaling molecules , which mediate signaling between cancer cells and the stromal environment .