Dickkopf-related protein 1 (DKK1) (DKK1)

Dickkopf-related protein 1 (DKK1) is a secreted protein that acts as a potent antagonist of the canonical Wnt/β-catenin signaling pathway [1]. It functions by binding to the LRP5/6 co-receptors and Kremen proteins, which induces the internalization of the LRP complex and prevents Wnt ligands from initiating downstream signaling [2]. In healthy physiology, DKK1 is a critical regulator of bone homeostasis, where it inhibits osteoblast differentiation and promotes bone resorption [3]. However, its overexpression is a hallmark of several pathologies, particularly multiple myeloma and various solid tumors, where it facilitates an immunosuppressive environment and promotes osteolytic bone lesions [4]. Therapeutic strategies, including the monoclonal antibody ALA-105, are designed to neutralize DKK1 to restore Wnt signaling, thereby stimulating anti-tumor immunity and mitigating bone loss [5].

Other names

DKK-1Dickkopf-1SK

DKK1 inhibitors, such as monoclonal antibodies, bind to the DKK1 protein to prevent its interaction with LRP5/6 and Kremen co-receptors. This neutralization restores the canonical Wnt/beta-catenin signaling pathway, which is often suppressed in diseases like multiple myeloma or bone loss conditions, thereby promoting osteoblast activity and enhancing anti-tumor immune responses.