1. Dickkopf signaling, beyond Wnt-mediated biology
- Author
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Shinji Matsumoto, Ryota Sada, and Akira Kikuchi
- Subjects
Adult ,musculoskeletal diseases ,Wnt signaling pathway ,Cancer ,Cell Biology ,Biology ,medicine.disease_cause ,medicine.disease ,Exosome ,Cell biology ,Adult life ,DKK1 ,Neoplasms ,medicine ,Humans ,Intercellular Signaling Peptides and Proteins ,Immune reaction ,Carcinogenesis ,Receptor ,Wnt Signaling Pathway ,Developmental Biology - 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.
- Published
- 2022
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