Dan family

Extracellular binding proteins or antagonists are important factors that modulate ligands in the transforming growth factor (TGF-β) family. Recent studies have implicated members of the differential screening-selected gene in neuroblastoma (DAN) family in disease such as renal fibrosis, pulmonary arterial hypertension, and reactivation of metastatic cancer stem cells. The family consists of seven members: Nbl1 (the founding member, also known as Dan and DAND1), SOST (Sclerostin), uterine sensitization-associated gene-1 (USAG-1/Wise), Coco (DAND5), Gremlin (Drm), Cerberus (Cer1), and protein related to Dan and Cerberus (PRDC/Gremlin-2). DAN family members are known to inhibit the bone morphogenetic proteins (BMP) of the TGF-β family. However, unlike other TGF-β antagonist families, DAN family members have roles beyond ligand inhibition and can modulate Wnt and vascular endothelial growth factor (VEGF) signaling pathways. Recently, DAN family proteins have been directly implicated in the reactivation of metastatic breast cancers within lung tissue. Therefore, DAN family proteins paly critical roles in human development and disease^[1].