A literature review on function and regulation mechanism of DKK4

Dickkopf‐related protein 4 (DKK4) is a member of the dickkopf family and an inhibitor of the Wnt/β‐catenin signalling pathway. This review surveyed the single nucleotide polymorphisms (SNPs), copy number variations (CNVs), hypermethylation, regulation mechanism, correlation with clinicopathological parameters and chemotherapeutic resistance of DKK4. The signal pathways involved in DKK4 mainly include Wnt/β‐catenin pathway and Wnt‐JNK pathway independent β‐catenin. DKK4 expression was upregulated in Renal Cell Carcinoma (RCC), Colorectal Cancer, Gastric Cancer (GC), Non‐small Cell Lung Cancer (NSCLC) and Epithelial Ovarian Cancer (EOC), while downregulated in Hepatocellular Carcinoma (HCC). DKK4 is not only involved in tumour growth, invasion, migration and chemotherapy resistance, but also in osteoblastogenesis and secondary hair or meibomian gland formation. DKK4 has also been linked to schizophrenia.