CDCP1

Fig1. The structure of CDCP1. (Xiao Qi, 2022)

What is CDCP1 protein?

CDCP1 gene (CUB domain containing protein 1) is a protein coding gene which situated on the short arm of chromosome 3 at locus 3p21. CDCP1 is a cell surface glycoprotein with three extracellular CUB domains and a transmembrane region. It plays a role in a variety of biological processes, including cell adhesion, cell-matrix interactions, and cell signaling regulation. CDCP1 is highly expressed in a variety of tumors, including kidney cancer, lung cancer, pancreatic cancer and breast cancer, and is closely related to the occurrence, development and prognosis of tumors. The CDCP1 protein is consisted of 836 amino acids and CDCP1 molecular weight is approximately 92.9 kDa.

What is the function of CDCP1 protein?

CDCP1 may be involved in adhesion between cells and extracellular matrix, affecting cell anchoring and migration. CDCP1 can act as a substrate of SRC-family kinases, participate in tyrosine phosphorylation-dependent cellular events, and regulate cell signaling. The expression and activity of CDCP1 may be regulated by the cell cycle and may affect the progression of the cell cycle. CDCP1 may play a role in cell differentiation, influencing cell fate decisions by regulating relevant signaling pathways. CDCP1 may be involved in the regulation of apoptosis, affecting cell survival and death.

CDCP1 Related Signaling Pathway

CDCP1 interacts with β1 integrin to promote tumor cell migration and invasion through the FAK/PI3K/Akt signaling pathway. CDCP1 enhances the Wnt signaling pathway and promotes nuclear localization of β-catenin and E-cadherin in colorectal cancer. CDCP1 interacts with other molecules in the tumor microenvironment, such as ADAM9, which enhances CDCP1 expression by inhibiting miR-1, thereby promoting lung cancer metastasis. In lung cancer, the AXL/CDCP1/SRC signaling axis is associated with acquired resistance to osimertinib. The expression of CDCP1 is regulated by mirnas such as miR-1, and the down-regulation of miRNA can enhance the expression of CDCP1 and promote the migration and stress resistance of tumor cells.

CDCP1 Related Diseases

CDCP1 is a cell surface transmembrane glycoprotein that is upregulated in a variety of malignant tumors. It involves many aspects of tumor, including tumor cell survival, growth, metastasis, and treatment resistance. CDCP1 is strongly associated with the progression of multiple cancers, including breast, lung, colorectal, ovarian, kidney, liver, pancreatic, and hematopoietic tumors. In these malignancies, high levels of CDCP1 expression are associated with advanced stages of disease, poorer prognosis, and/or reduced responsiveness to treatment, suggesting a functional role for it in disease progression.

Bioapplications of CDCP1

CDCP1 can be detected in the serum, urine and other body fluids of patients, and its elevated level is closely related to the diagnosis and prognosis of many cancers. For example, patients with colorectal and stomach cancer had significantly elevated levels of CDCP1 in their serum, and prostate cancer patients showed a similar phenomenon in their urine. CDCP1 is considered a potential therapeutic target. By blocking CDCP1 signaling or using it as a carrier to deliver drugs directly to tumor cells, tumor growth and metastasis can be inhibited. Using CDCP1 as a target, PET radiotracers for cancer imaging can be developed.

Case Study 1: Fumihiko Urabe, 2023

Bone metastases are still incurable and result in the development of clinical complications and decreased survival for prostate cancer patients. Recently, a number of studies have shown that extracellular vesicles (EVs) play important roles in tumour progression. In this study, EVs from metastatic prostate cancer cells promote osteoclast formation in the presence of receptor activator of NF-κB ligand (RANKL). EV characterization followed by functional siRNA screening identified CUB-domain containing protein 1 (CDCP1). Additionally, CDCP1 expression on plasma-derived EVs was upregulated in bone metastatic prostate cancer patients.

Fig1. EVs from PC3M and PNT2 cells were analysed by immunoblotting.

Fig2. Immunoelectron microscopy images of HEK293 cell-derived EVs labelled with anti-CDCP1 antibody.

Case Study 2: Shion A Lim, 2022

Extracellular proteolysis is frequently dysregulated in disease and can generate proteoforms with unique neoepitopes not found in healthy tissue. This study demonstrates that Abs that selectively recognize a proteolytic neoepitope on CUB domain containing protein 1 (CDCP1) could enable more effective and safer treatments for solid tumors. CDCP1 is highly overexpressed in RAS-driven cancers, and its ectodomain is cleaved by extracellular proteases. Biochemical, biophysical, and structural characterization revealed that the 2 cleaved fragments of CDCP1 remain tightly associated with minimal proteolysis-induced conformational change. Using differential phage display, researchers generated recombinant Abs that are exquisitely selective to cleaved CDCP1 with no detectable binding to the uncleaved form. These Abs potently targeted cleaved CDCP1-expressing cancer cells as an Ab-drug conjugate, an Ab-radionuclide conjugate, and a bispecific T cell engager. Targeting proteolytic neoepitopes could provide an orthogonal "AND" gate for improving the therapeutic index.

Fig3. SDS-PAGE of CDCP1 constructs.

Fig4. BLI shows specific binding of IgG CL03 to c-CDCP1-Fc, but not to fl-CDCP1-Fc.

CDCP1 has several biochemical functions, for example, protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by CDCP1 itself. We selected most functions CDCP1 had, and list some proteins which have the same functions with CDCP1. You can find most of the proteins on our site.

CDCP1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with CDCP1 here. Most of them are supplied by our site. Hope this information will be useful for your research of CDCP1.

PRKCD;SRC;SDCBP;YES1;EGFR;ALB