CUB Domain Containing Protein 1, known as CDCP1, is a protein found in the human body. Research has revealed its involvement in various cellular processes. Understanding its normal functions and how its behavior can change is a focus for scientists.
What is CDCP1
CDCP1 is a transmembrane protein situated on the surface of cells. Its structure includes a large extracellular domain that protrudes outside the cell, and a smaller intracellular domain that resides inside. The extracellular portion contains two CUB domains, protein modules often involved in protein-protein interactions.
CDCP1 is expressed in various human tissues, including the gingival epithelium, islets of Langerhans, and mucosal linings like those in the esophagus, transverse colon, and rectum. It is also detected in cartilage, hair follicles, and pancreatic ductal cells. CDCP1 exists in two main forms: a full-length 140 kDa molecule and an 80 kDa truncated version, produced when serine proteases cleave its extracellular domain.
How CDCP1 Functions in Healthy Cells
In healthy cells, CDCP1 participates in physiological processes, influencing how cells interact and respond to their environment. It is involved in cell adhesion, the process by which cells attach to one another and to the surrounding extracellular matrix. This adhesion helps maintain tissue structure and organization.
CDCP1 also contributes to cell signaling pathways, relaying messages within and between cells. Its intracellular domain contains tyrosine residues that can be phosphorylated, a modification that often initiates or modulates cellular signals. This signaling can influence cell proliferation, the rate at which cells grow and divide, and differentiation, the process by which cells become specialized.
CDCP1 plays a part in cell migration, the directed movement of cells, a process important for wound healing and immune responses. In corneal epithelial cells, CDCP1 cleavage by serine proteases like plasmin helps regulate growth factors such as VEGF-A and EGF, important for wound closure. When CDCP1 activity is reduced, wound healing can be delayed.
CDCP1’s Role in Cancer
In various types of cancer, CDCP1’s function or expression can be altered, contributing to disease progression. It is often overexpressed, meaning it is present in abnormally high amounts, in many human cancers, including breast, lung, colon, ovary, kidney, liver, pancreas, and hematopoietic system. This overexpression is frequently linked to more advanced disease stages and poorer patient outcomes.
CDCP1 contributes to tumor growth by influencing signaling pathways that promote cell survival and proliferation, such as SRC/PKCĪ“, PI3K/AKT, WNT, and RAS/ERK. For example, in prostate cancer, CDCP1 overexpression, particularly when combined with PTEN loss, can accelerate tumor progression and lead to metastatic disease. CDCP1 can also facilitate metastasis, the spread of cancer cells to distant parts of the body, by promoting cell migration and anchorage-independent growth, which allows cancer cells to survive and proliferate without being attached to a surface. In melanoma, elevated CDCP1 levels are associated with increased metastatic potential.
Beyond growth and spread, CDCP1’s altered expression can also contribute to resistance to certain cancer therapies. In lung cancer with specific EGFR mutations, co-expression of CDCP1 and Axl can reduce the effectiveness of EGFR-targeted tyrosine kinase inhibitors. Similarly, this co-expression has been observed to mediate resistance to nilotinib, a drug used for chronic myeloid leukemia. CDCP1’s involvement in these processes makes it a focus in cancer research.
Targeting CDCP1: Research and Therapeutic Potential
Research is exploring CDCP1 as a target for cancer diagnosis and therapy. Its elevated expression in many malignancies makes it a biomarker for detecting cancer or predicting its course. Studies are evaluating CDCP1 as a tracer target for medical imaging or as a marker detectable in bodily fluids for early cancer diagnosis.
Scientists are also investigating strategies to therapeutically target CDCP1 to combat cancer. One approach involves antibody-drug conjugates (ADCs), where an antibody binds to CDCP1 on cancer cells and delivers a cytotoxic drug directly. For example, an anti-CDCP1 antibody conjugated to a tubulin polymerization inhibitor, MMAE, has shown effectiveness in reducing tumor growth and improving survival in mouse models of ovarian and pancreatic cancer.
Another strategy involves inhibitors aimed at blocking CDCP1’s activity, potentially by targeting its proteolytic cleavage or downstream signaling pathways. Preclinical studies have shown that anti-CDCP1 immunoliposomes, drug-carrying nanoparticles loaded with chemotherapy, can suppress prostate cancer growth when combined with existing treatments like enzalutamide. These investigations show the potential for CDCP1-directed therapies to offer new avenues for cancer treatment.