The protein known as TACSTD2, or TROP2, is a cell surface receptor found on various cells throughout the human body. It plays a role in communication networks that govern cell behavior. Researchers are increasingly focusing on TROP2 due to its involvement in numerous biological processes. Understanding its functions and dysfunctions offers new avenues for medical research, particularly in the study and treatment of various diseases.
Understanding TACSTD2
TACSTD2 is a gene that produces the protein commonly referred to as TROP2. This protein is a type I transmembrane glycoprotein, embedded within the cell membrane, with portions extending both inside and outside the cell. TROP2 is approximately 35-36 kDa in size and is also known as epithelial glycoprotein-1 (EGP-1) and gastrointestinal tumor-associated antigen GA7331.
The TACSTD2 gene, which is intronless, is located on the short arm of chromosome 1 at 1p32.1. TROP2 is a member of a protein family that includes at least two type I membrane proteins, with EpCAM (epithelial cell adhesion molecule) being another member. TROP2 and EpCAM share structural and sequence similarities, with TROP2 exhibiting about 49% homology with EpCAM.
TACSTD2’s Normal Functions
In healthy cells, TROP2 performs several roles, contributing to proper physiological processes. It participates in cell-to-cell adhesion, helping cells stick together to form tissues. TROP2 also influences cell growth, proliferation, and differentiation.
The protein transduces intracellular calcium signals. This signaling mechanism allows TROP2 to influence various pathways that regulate cell behavior. Its presence is important during embryonic development and for the maintenance of various tissues.
TACSTD2 and Disease
Dysregulation or overexpression of TROP2 is frequently associated with various diseases, particularly cancer. TROP2 is found at elevated levels in many solid tumors, including breast, lung, ovarian, and colorectal cancers. Its overexpression has also been noted in less common but aggressive malignancies like salivary duct and anaplastic thyroid cancers.
The increased presence of TROP2 in cancer cells can contribute to several aspects of tumor progression. It can promote uncontrolled tumor growth, facilitate metastasis—the spread of cancer cells from the primary site to other parts of the body—and contribute to resistance against certain cancer treatments. For instance, TROP2 promotes cell proliferation and migration in gallbladder cancer cells. Overexpression of TROP2 is also linked to poor prognosis in patients with cervical cancer, as it promotes the proliferation and invasion of these cells.
Targeting TACSTD2 in Treatment
Given its frequent overexpression in various cancers, TROP2 has emerged as a promising target for therapeutic interventions. One primary strategy involves developing antibody-drug conjugates (ADCs) that specifically recognize and bind to TROP2-expressing cancer cells. These ADCs deliver a potent chemotherapy drug directly to tumor cells while minimizing harm to healthy tissues.
An ADC typically consists of an antibody that targets TROP2 linked to a chemotherapy agent. Once the antibody binds to TROP2 on the surface of a cancer cell, the complex is internalized. Inside the cell, the chemotherapy drug is released, leading to the cancer cell’s death. Clinical studies are underway to evaluate the effectiveness of TROP2-targeting ADCs, such as sacituzumab govitecan and datopotamab deruxtecan (Dato-DXd), in patients with various epithelial cancers. These therapies hold the potential to improve treatment outcomes for individuals battling TROP2-positive cancers.