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Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2)
- Target
- DCBLD2
- Molecular classification
- Receptor (type-I transmembrane receptor), Neuropilin-like protein, Cell adhesion molecule (shares structural similarity to neuropilins and involves discoidin, CUB, and LCCL domains)
01
Overview
Discoidin, CUB and LCCL domain-containing protein 2 (DCBLD2) is a type-I transmembrane receptor characterized by the presence of discoidin, CUB, and LCCL domains, structurally similar to neuropilins. DCBLD2 is predominantly expressed in endothelial and vascular smooth muscle cells, as well as in various tissues including the brain and heart. It plays significant roles in angiogenesis, cell proliferation, migration, EMT, and vascular remodeling. DCBLD2 functions as a surface receptor for semaphorin 3 and growth factors, modulating intracellular signaling relevant to cancer progression (notably colorectal cancer), resistance to chemotherapies such as 5-FU, and vascular pathologies. Overexpression is commonly associated with poor prognosis in cancer and enhanced resistance to anticancer drugs, making it a potential therapeutic target and biomarker candidate, particularly in oncology and vascular disease contexts.
- Other names
- CLCP1ESDNCUB, LCCL and coagulation factor V/VIII-homology domains protein 1Endothelial and smooth muscle cell-derived neuropilin-like protein1700055P21Rik
02
Mechanism of action
Drug sensitivity modulation: DCBLD2 overexpression confers resistance to 5-FU by promoting cell proliferation, migration, EMT, and angiogenesis
03
Biological functions
Regulation of cell proliferationCell migration and motilityAngiogenesisSignal transduction (intracellular receptor signaling pathways)Epithelial-mesenchymal transition (EMT)Vascular smooth muscle cell (VSMC) regulationNeuronal positioning
04
Disease associations
Cancer (notably colorectal cancer, lung cancer, other solid tumors)Cardiovascular disease (vascular remodeling, arterial hyperplasia)Neurodevelopmental disorders (emerging evidence)Metabolic diseases (suggested)
05
Safety considerations
Targeting DCBLD2 could impact vascular biology and normal angiogenesis, as it is expressed in endothelial and smooth muscle cells and is involved in vascular remodelingPotential off-target or systemic effects due to its broad expression and role in cell growth, vascular development, and neural positioning
06
Interacting drugs
5-Fluorouracil (5-FU; increased resistance to this chemotherapy drug when DCBLD2 is overexpressed, especially in colorectal cancer)
07
Biomarkers
High DCBLD2 expression is a marker of poor prognosis and 5-FU resistance in colorectal cancer patients
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