Creative Biogene Creative Biogene
Inquiry
Pages
Products
  1. Home
  2. Search Results for "dll3"

DLL3

Official Full Name
delta like canonical Notch ligand 3
Organism
Homo sapiens
GeneID
10683
Background
This gene encodes a member of the delta protein ligand family. This family functions as Notch ligands that are characterized by a DSL domain, EGF repeats, and a transmembrane domain. Mutations in this gene cause autosomal recessive spondylocostal dysostosis 1. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
Synonyms
SCDO1;
Protein Sequence
MVSPRMSGLLSQTVILALIFLPQTRPAGVFELQIHSFGPGPGPGAPRSPCSARLPCRLFFRVCLKPGLSEEAAESPCALGAALSARGPVYTEQPGAPAPDLPLPDGLLQVPFRDAWPGTFSFIIETWREELGDQIGGPAWSLLARVAGRRRLAAGGPWARDIQRAGAWELRFSYRARCEPPAVGTACTRLCRPRSAPSRCGPGLRPCAPLEDECEAPLVCRAGCSPEHGFCEQPGECRCLEGWTGPLCTVPVSTSSCLSPRGPSSATTGCLVPGPGPCDGNPCANGGSCSETPRSFECTCPRGFYGLRCEVSGVTCADGPCFNGGLCVGGADPDSAYICHCPPGFQGSNCEKRVDRCSLQPCRNGGLCLDLGHALRCRCRAGFAGPRCEHDLDDCAGRACANGGTCVEGGGAHRCSCALGFGGRDCRERADPCAARPCAHGGRCYAHFSGLVCACAPGYMGARCEFPVHPDGASALPAAPPGLRPGDPQRYLLPPALGLLVAAGVAGAALLLVHVRRRGHSQDAGSRLLAGTPEPSVHALPDALNNLRTQEGSGDGPSSSVDWNRPEDVDPQGIYVISAPSIYAREVATPLFPPLHTGRAGQRQHLLFPYPSSILSVK
Open
Disease
Lung cancer, Solid tumour/cancer, Stomach cancer
Approved Drug
0
Clinical Trial Drug
6 +
Discontinued Drug
0

Detailed Information

The Notch pathway is a highly conserved cell-cell signaling pathway, involved in multiple development processes, including the development of pulmonary neuroendocrine cells. Delta-like ligand 3 (DLL3) is an inhibitory Notch pathway ligand, which is highly upregulated and aberrantly expressed on the cell surface in small-cell lung cancer (SCLC) and other high-grade neuroendocrine tumors. As a key mediator of cellular development, DLL3 inhibits Notch pathway activation by redirecting or retaining the Notch and Notch activating ligand DLL1 to the late endosomal/lysosomal compartments or the Golgi, respectively, and preventing their localization to the cell surface. The cell surface Notch ligand DLL3 has recently become a therapeutic target in cancer, pioneered in pulmonary neuroendocrine tumors.

Overview of DLL3

The Notch pathway plays an important role in regulating neuroendocrine and epithelial cell fate decisions in the developing lung. The mammalian Notch family ligands DLL1, DLL4, JAG1, and JAG2 each activate Notch receptor signaling in trans. However, compared with DLL1 (and the other Notch ligands), DLL3 expressed in cultured cells cannot activate Notch on adjacent cells in vitro and, in vivo DLL3 protein expressed instead of DLL1 in mouse embryos did not activate Notch under physiological conditions and could not compensate for DLL1 loss. DLL1 is located on the cell surface, while DLL3 resides almost exclusively in the Golgi apparatus both in PSM cells and when overexpressed in cultured cells, and was suggested to cis-inhibit Notch1 in the PSM through directing full-length Notch1 to late endosome/lysosomes and preventing its S1 processing. Normal tissue expression of DLL3 is highest in the fetal brain, and DLL3 plays a critical role in somitogenesis in the paraxial mesoderm. Although Notch pathway activation acts as an oncogenic stimulus in some tumor types, Notch activation in neuroendocrine tumors inhibits tumor growth. During normal development, DLL3 inhibits both cis- and trans-acting Notch pathway activation by interacting with Notch and DLL1 and redirecting or retaining them to late endosomal/lysosomal compartments or the Golgi, respectively, thus preventing their localization to the cell surface. In addition, DLL3 is one of several Notch ligands that seem to be direct downstream targets of ASCL1. In conclusion, these observations show that DLL3 might be associated with the neuroendocrine phenotype and contributes to neuroendocrine tumorigenesis.

DLL3 and Small-Cell Lung Cancer

DLL3 has been identified in tumour-initiating cells isolated from SCLC. DLL3 is specifically expressed on the surface of SCLC cells. In 10 SCLC and 1 large cell neuroendocrine carcinoma (LCNEC) patient-derived xenograft models, DLL3 surface expression correlated with time to tumor progression. It is expressed on the surface of tumour cells in about 85% of patients with SCLC and large-cell neuroendocrine cancer, and cytoplasmic and membranous staining of DLL3 was observed by IHC with a high level of homogeneity across neoplastic cells. In contrast, only a few normal cell types expressed DLL3 (e.g., neurons, pituitary cells, and pancreatic islet cells), and expression of DLL3 was exclusively cytoplasmic. Recent studies have shown that DLL3 is also expressed in other tumor types of neuroendocrine origin, including glioblastoma multiforme, melanoma, small cell bladder cancer, neuroendocrine lung tumors and metastatic castration-resistant prostate cancer. The DLL3 expression profile—high, homogeneous cell surface expression in tumors, versus low, cytoplasmic expression in a subset of normal tissues—has allowed the development of therapeutics that use DLL3 to specifically target SCLC cells. These DLL3-specific agents are now being evaluated in several ongoing clinical researches in SCLC and other neuroendocrine tumors.

DLL3Figure 1. DLL3-targeted investigational products utilize distinct mechanisms of action. (Owen D H, et al., 2019)

References:

  1. Spino M, et al. Cell Surface Notch Ligand DLL3 is a Therapeutic Target in Isocitrate Dehydrogenase–mutant Glioma. Clinical Cancer Research, 2019, 25(4): 1261-1271.
  2. Rossi A. Rovalpituzumab tesirine and DLL3: a new challenge for small-cell lung cancer. The Lancet Oncology, 2017, 18(1): 3-5.
  3. Sharma S K, et al. Noninvasive interrogation of DLL3 expression in metastatic small cell lung cancer. Cancer research, 2017, 77(14): 3931-3941.
  4. Serth K, et al. O-fucosylation of DLL3 is required for its function during somitogenesis. PloS one, 2015, 10(4): e0123776.
  5. Owen D H, et al. DLL3: an emerging target in small cell lung cancer. Journal of hematology & oncology, 2019, 12(1): 1-8.
  6. Saunders L R, et al. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Science translational medicine, 2015, 7(302): 302ra136-302ra136.
Quick Inquiry

Receive a quote or more information about stable cell line generation services.

If you don’t find the cell line you want, Creative Biogene can also provide stable cell line generation service with the best prices and fastest turnaround time for you! Contact us for more information or to request a quote.

Request a quote today!

Inquiry

Products

Transfected Stable Cell Lines

Premade Virus Particles

Laboratory Equipment

RNA Interference Products

Cell Lysate

Clones

Enzymes

Kits

Aptamers

Services

Stable Cell Line Generation

Target-based Drug Discovery Service

Custom Libraries Construction Service

Microbe Genome Editing Service

Biosafety Testing Service

Nucleotides Service

MicroRNA Service

RNAi Service

Custom Viral Service

Platforms

CRISPR/Cas9 PlatformCB

QvirusTM Platform

IntegrateRNA Platform

Microbiology Platform

Zebrafish Platform

Get in Touch

Tel

1-631-626-9181 (USA)

44-208-123-7131 (Europe)

Fax

1-631-614-7828

Email

info@creative-biogene.com

USA

SUITE 115, 17 Ramsey Road, Shirley, NY 11967, USA

Germany

Industriepark Höchst, Gebäude G830 65929 Frankfurt am Main

Copyright © 2025 Creative Biogene. All rights reserved.

Privacy Policy | Cookie Policy

We use cookies to understand how you use our site and to improve the overall user experience. This includes personalizing content and advertising. Read our Privacy Policy

x