Dickkopf signaling, beyond Wnt-mediated biology. (May 2022)

• Record Type: Journal Article
• Authors: Kikuchi, Akira; Matsumoto, Shinji; Sada, Ryota
• Is Part Of: Seminars in cell & developmental biology. Volume 125(2022)
• Page Start: 55
• Page End: 65
• Publication Date: 2022-05
• Subjects: DKK Dickkopf -- LRP LDL receptor-related protein -- TCF T-cell factor -- LEF lymphocyte enhancer factor -- sFRP soluble Frizzled-related protein -- WIF-1 Wnt inhibitory factor-1 -- CRD cysteine-rich domain -- WSC cell wall stress-responsive component -- CUB complement, C1r/C1s, Uegf, Bmp1 -- CKAP4 cytoskeleton associated protein 4 -- ER endoplasmic reticulum -- ERGIC ER-to-Golgi intermediate compartment -- COP coat protein complex -- APT acyl-protein thioesterase -- ICC intrahepatic cholangiocarcinoma -- HCC hepatocellular carcinoma -- FOX forkhead box -- CRC colorectal cancer -- MM multiple myeloma -- mAb monoclonal antibody -- G/GEJ gastric and gastroesophageal junction -- KO knockout -- ELISA enzyme-linked immunosorbent assay -- ORP overall response rate -- MVB multivesicluar body -- RPPA reverse-phase protein assay -- VEGF vascular endothelial growth factor -- PLVAP plasmalemma vesicle-associated protein -- dMMR deficient mismatch repair -- MSI microsatellite-instability -- LLC Lewis lung carcinoma -- MDSC myeloid-derived suppressor cell -- NK natural killer -- NSG NOD scid gamma -- APC adenomatous polyposis coli -- GIST gastrointestinal stromal tumor; Dickkopf -- Wnt -- CKAP4 -- Molecular target -- Exosome; Cytology -- Periodicals; Developmental biology -- Periodicals; 571.6
• DOI: 10.1016/j.semcdb.2021.11.003
• Languages: English
• ISSNs: 1084-9521

Abstract

Abstract: Dickkopf1 (DKK1) was originally identified as a secreted protein that antagonizes Wnt signaling. Although DKK1 is essential for the developmental process, its functions in postnatal and adult life are unclear. However, evidence is accumulating that DKK1 is involved in tumorigenesis in a manner unrelated to Wnt signaling. In addition, recent studies have revealed that DKK1 may control immune reactions, although the relationship of this to Wnt signaling is unknown. Other DKK family members, DKK2–4, are likely to have their own functions. Here, we review the possible novel functions of DKKs. We summarize the characteristics of receptors of DKKs and the signaling mechanisms through DKKs and their receptors, provide evidence showing that DKKs are involved in tumor aggressiveness independently of Wnt signaling, and emphasize promising cancer therapies targeting DKKs and receptors. Lastly, we discuss various physiological and pathological processes controlled by DKKs.