DKK1 (Dickkopf-related protein 1) is a secreted glycoprotein that acts as a key antagonist of the Wnt/β-catenin signaling pathway, a critical regulator of embryonic development, tissue homeostasis, and cancer progression. By binding to the LRP5/6 co-receptors, DKK1 inhibits Wnt signaling, leading to reduced β-catenin stabilization and downstream gene expression. Dysregulation of DKK1 has been implicated in various diseases, including osteoporosis, rheumatoid arthritis, neurodegenerative disorders, and multiple cancers (e.g., multiple myeloma, breast, and lung cancers), where it often promotes tumor growth, angiogenesis, or immune evasion.
DKK1 antibodies are therapeutic or research tools designed to neutralize DKK1 activity, thereby restoring Wnt signaling. In oncology, anti-DKK1 antibodies may inhibit tumor proliferation, enhance bone formation in osteolytic lesions, and synergize with chemotherapy or immunotherapy. In bone diseases, they are explored to counteract DKK1-mediated suppression of osteoblast differentiation. Additionally, elevated DKK1 levels in cerebrospinal fluid or serum are studied as potential biomarkers for Alzheimer’s disease or certain cancers.
Developed as monoclonal antibodies (e.g., DKN-01 in clinical trials) or recombinant proteins, DKK1-targeting agents face challenges related to tissue specificity and signaling crosstalk. Nonetheless, they represent a promising strategy for modulating Wnt pathway activity in both mechanistic studies and therapeutic applications.