Delta-like non-canonical Notch ligand 1 (DLK1) (DLK1)

Delta-like non-canonical Notch ligand 1 (DLK1), also known as Preadipocyte factor 1 (Pref-1), is a transmembrane protein characterized by six epidermal growth factor (EGF)-like repeats in its extracellular domain [UniProt: P80370]. It functions as a non-canonical ligand for the Notch signaling pathway, where it typically acts as an antagonist to Notch receptor activation, thereby maintaining cells in an undifferentiated, progenitor-like state [PubMed: 22561082]. DLK1 is highly expressed during fetal development but its expression becomes highly restricted in adults, primarily localized to the pituitary gland, adrenal cortex, and pancreatic islets [PubMed: 24035544]. In the context of metabolism, DLK1 is a potent inhibitor of adipogenesis, preventing the differentiation of mesenchymal stem cells into mature adipocytes [PubMed: 10648609]. In clinical oncology, DLK1 is frequently overexpressed in various malignancies, including hepatocellular carcinoma, neuroblastoma, and small cell lung cancer, where it promotes tumor cell proliferation and stemness [PubMed: 28651544]. This restricted expression pattern in normal adult tissues compared to high expression in tumors makes DLK1 an attractive therapeutic target. Current drug development efforts focus on monoclonal antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR) T-cell therapies designed to selectively eliminate DLK1-positive cancer cells [PubMed: 31110039]. Additionally, DLK1 is an imprinted gene, and its dysregulation is linked to developmental disorders such as Temple syndrome and Kagami-Ogata syndrome [PubMed: 25033325].

Other names

Preadipocyte factor 1Pref-1Fetal antigen 1FA1ZOGpG2

Non-canonical inhibition of Notch signaling and suppression of adipogenic transcription factors