Dickkopf 信号通路，超越 Wnt 介导的生物学。

Dickkopf signaling, beyond Wnt-mediated biology.

机构信息

Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita 565-0871, Osaka, Japan.

Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Suita 565-0871, Osaka, Japan; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, 2-2 Yamada-oka, Suita 565-0871, Osaka, Japan.

出版信息

Semin Cell Dev Biol. 2022 May;125:55-65. doi: 10.1016/j.semcdb.2021.11.003. Epub 2021 Nov 18.

DOI:10.1016/j.semcdb.2021.11.003

PMID:34801396

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.

摘要

Dickkopf1（DKK1）最初被鉴定为一种能拮抗 Wnt 信号的分泌蛋白。虽然 DKK1 对发育过程是必需的，但它在出生后和成年生活中的功能尚不清楚。然而，越来越多的证据表明 DKK1 通过与 Wnt 信号无关的方式参与肿瘤发生。此外，最近的研究表明，DKK1 可能控制免疫反应，尽管这与 Wnt 信号的关系尚不清楚。其他 DKK 家族成员 DKK2-4 可能具有各自的功能。在这里，我们综述了 DKKs 的可能的新功能。我们总结了 DKKs 的受体的特征以及通过 DKKs 和其受体的信号机制，提供了 DKKs 独立于 Wnt 信号参与肿瘤侵袭的证据，并强调了针对 DKKs 和受体的有前途的癌症治疗方法。最后，我们讨论了 DKKs 控制的各种生理和病理过程。