Dickkopf-1 (DKK-1) is a well-established inhibitor of canonical Wnt-signaling that critically participates in the regulation of bone formation and has been implicated in the development and progression of bone metastases. While the skeleton was originally considered the sole site of DKK-1 synthesis, it has now become clear that the molecule is also highly expressed in T-cells, platelets and multiple cancer cells. In the past years, several new functions of DKK-1 in angiogenesis, cancer cell biology, immune homeostasis and inflammation have been revealed. These novel insights have paved the way for clinical trials investigating the efficacy of anti-DKK-1 antibodies in a variety of different malignancies, most of which are currently still ongoing. In this review, we discuss the evolution and recent advances in DKK-1 research and highlight clinical implications of the available knowledge on the molecule, especially in cancer. Finally, we emphasize outstanding questions and provide an outlook on potential future studies that will aid in further improving our understanding of the pleiotropic roles of DKK-1 in health and disease.

中文翻译：

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Dickkopf-1在癌症和免疫中的功能不断发展。

Dickkopf-1（DKK-1）是一种完善的经典Wnt信号抑制剂，主要参与骨形成的调节，并参与了骨转移的发生和发展。虽然骨架最初被认为是DKK-1合成的唯一位点，但现在已经清楚该分子在T细胞，血小板和多种癌细胞中也高度表达。在过去的几年中，DKK-1在血管生成，癌细胞生物学，免疫稳态和炎症中已揭示了几种新功能。这些新颖的见解为研究抗DKK-1抗体在各种不同恶性肿瘤中的功效的临床试验铺平了道路，其中大多数目前仍在进行中。在这篇评论中 我们讨论了DKK-1研究的进展和最新进展，并重点介绍了有关分子的可用知识的临床意义，尤其是在癌症中。最后，我们强调悬而未决的问题，并对未来的潜在研究提供展望，这将有助于进一步增进我们对DKK-1在健康和疾病中的多效性作用的理解。