DKK4

DKK4, or Dickkopf-related protein 4, is a secreted glycoprotein that belongs to the Dickkopf family of Wnt signaling antagonists. The DKK4 gene encodes this protein in humans. The Dickkopf proteins regulate the Wnt/beta-catenin signaling pathway, which governs cell fate, proliferation, and tissue patterning during development and in maintaining homeostasis. DKK4 inhibits canonical Wnt signaling by binding to the co-receptors LRP5 and LRP6 and by interacting with Kremen1/2, which promotes internalization of the LRP coreceptors and reduces Wnt signal transduction. Structurally, DKK4 shares features with other family members, including an N-terminal signal peptide for secretion and a cysteine-rich domain important for receptor interaction.

Expression of DKK4 occurs in a range of tissues, with reports of enrichment in the digestive tract and placenta, though levels vary by tissue and developmental context. Its expression can be influenced by developmental cues and epigenetic mechanisms, such as promoter methylation, which can affect levels in disease settings.

In human disease, DKK4 has been studied as a potential biomarker and therapeutic target due to its role in Wnt signaling. Altered DKK4 expression has been reported in several cancers, including colorectal, gastric, and hepatocellular carcinoma, with studies showing both upregulation and downregulation depending on tissue and context. Some findings have linked DKK4 expression to prognosis or treatment response, but robust clinical utility has not been established.