Nectin-4 is a protein found in the human body, playing a part in how cells interact with each other. This protein contributes to fundamental biological processes, including cell communication and the maintenance of tissue structure.
Understanding Nectin-4
Nectin-4 is a cell adhesion molecule, meaning it helps cells stick together. It is a transmembrane protein.
Structurally, Nectin-4 features an extracellular region composed of three immunoglobulin-like domains. It also possesses a transmembrane domain that anchors it to the cell membrane and a cytoplasmic domain that can bind to proteins involved in cell signaling.
Normal Functions of Nectin-4
Nectin-4 plays a role in cell-to-cell adhesion, which is important for maintaining the integrity of tissues throughout the body. It forms physical connections between neighboring cells, contributing to the overall organization and stability of cellular structures. These interactions can occur between identical Nectin-4 molecules or with other Nectin family members.
This protein also participates in cell signaling pathways that regulate various cellular activities. It influences processes such as cell growth, differentiation, and migration. While Nectin-4 is expressed at very low levels in most healthy adult tissues, it is specifically expressed during embryonic and fetal development, particularly in the placenta.
Nectin-4’s Role in Cancer Development
The expression and function of Nectin-4 can become altered in various cancers, where it is often found at significantly elevated levels compared to healthy tissues. This overexpression has been observed in several tumor types, including breast, ovarian, lung, bladder, pancreatic, and gastric cancers. High Nectin-4 expression is frequently associated with tumor progression and a less favorable outlook for patients.
Nectin-4 contributes to cancer progression through several mechanisms. It can promote tumor cell proliferation, migration, and survival. For instance, Nectin-4 can enhance tumor angiogenesis, which is the formation of new blood vessels that supply tumors with nutrients, often through activation of the PI3K/AKT signaling pathway. Additionally, Nectin-4 has been linked to epithelial-mesenchymal transition (EMT), a process that allows cancer cells to become more migratory and invasive, contributing to metastasis.
Targeting Nectin-4 in Cancer Treatment
Given its overexpression in many cancers and its limited presence in healthy adult tissues, Nectin-4 has emerged as a promising target for cancer treatment. Therapeutic strategies that leverage Nectin-4 as a target often involve antibody-drug conjugates (ADCs). These specialized drugs are designed to deliver chemotherapy directly to cancer cells.
An example of such an ADC is enfortumab vedotin (EV), which specifically targets Nectin-4. This ADC consists of an antibody that recognizes Nectin-4, linked to a potent chemotherapy agent called monomethyl auristatin E (MMAE). When EV binds to Nectin-4 on the surface of cancer cells, it is internalized, and the MMAE is released inside the cell, leading to the death of the cancer cell. Enfortumab vedotin has been approved by the FDA for the treatment of locally advanced or metastatic urothelial carcinoma. Researchers are also exploring other therapeutic avenues targeting Nectin-4, such as immunotherapy and gene therapy, and investigating its potential in other solid tumors.