DLK1 (F8J8Y) Rabbit mAb #32146

Delta-like-1 homolog (DLK1), also known as fetal antigen 1 (FA1) and preadipocyte factor 1 (pref-1), is a member of the epidermal growth factor (EGF)-like family of proteins, containing six tandem EGF-like repeats (1,2). DLK1 is a paternally expressed, imprinted gene that plays an important role in normal development and in the maintenance of homeostasis of adipose tissue mass (3). DLK1-deficient mice display growth retardation, obesity, skeletal malformation, and increased serum lipid metabolites (4). It has been reported that the ectodomain of DLK1 is shredded from the cell surface and inhibits adipocyte differentiation (5-7).

Humans and rodents express multiple isoforms of DLK1, which are either membrane bound or contain an ADAM17/TACE cleavage site for release of the soluble ectodomain (8). As high DLK1 expression is pro-oncongenic in some contexts, differential isoform expression may promote cancer cell survival, with both the ectodomain and intracellular domain having distinct functions (9). Under hypoxic conditions, HIF proteins induce ADAM17/TACE cleavage and internalization of the DLK1 intracellular domain, which localizes to the nucleus and alters Akt and p53 signaling cascades in glioma (10). Hypoxia increases DLK1 expression, and phosphorylation of the DLK1 C-terminus at Tyr339 and Ser355 increases neuronal tumor sphere growth (11). Nuclear DLK1 directly interacts with tumor supressor NCoR1, correlating with poor prognosis in non small cell lung cancer (NSCLC) (12). DLK1 has emereged as a target for novel antibody drug conjugates (ADCs) in neuroblastoma and adrenocortical carcinoma (13, 14).