THBS1

Fig1. Domain structure of TSP1 and its regional specific mimetic peptides and their function. (Bo Liu, 2024)

What is THBS1 Protein?

THBS1 gene (thrombospondin 1) is a protein coding gene which situated on the long arm of chromosome 15 at locus 15q14. The protein encoded by this gene is a subunit of a disulfide-linked homotrimeric protein. This protein is an adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1. This protein has been shown to play roles in platelet aggregation, angiogenesis, and tumorigenesis. The THBS1 protein is consisted of 1170 amino acids and THBS1 molecular weight is approximately 129.4 kDa.

What is the Function of THBS1 Protein?

THBS1 is a multifunctional extracellular matrix protein and a member of the Thrombospondin family. It plays a role in a variety of biological processes, including cell adhesion, migration, proliferation, and regulation of cell survival. The role of THBS1 in the tumor microenvironment is multifaceted, it can inhibit angiogenesis, regulate anti-tumor immune response, stimulate tumor cell migration, and affect the activity of extracellular proteases and growth factors. In addition, THBS1 plays a regulatory role in tumor response to therapeutic radiation and chemotherapy.

Fig2. Effects of TSP1 and ligands in glucose metabolism and diabetes mellitus. (Linda S Gutierrez, 2021)

THBS1 Related Signaling Pathway

Thbs1-related signaling pathways are mainly involved in tumor development, cardiovascular stress response, tumor immune escape, and various cell signal transduction pathways. THBS1 is a member of the platelet reactive protein family, which plays an important role in several biological processes. During tumor development, THBS1 supports tumor cell adhesion and invasion by interacting with transforming growth factor β (TGF-β). At the same time, THBS1 also plays an important role in cardiovascular diseases, for example, under cardiac injury or stress response, THBS1 expression increases significantly and participates in the formation process of heart hypertrophy.

THBS1 Related Diseases

THBS1 is commonly associated with tumor development, cardiovascular disease, immunomodulatory and metabolic diseases. In nonalcoholic fatty liver disease, THBS1 serves as a novel biomarker whose levels are elevated in patients' serum and correlated with liver fat content. In addition, THBS1 expression in glioblastoma is associated with poorer patient outcomes and may influence the tumor microenvironment by regulating macrophage M0 infiltration. In laryngeal cancer, THBS1 is related to the migration, invasion and proliferation of tumor cells, and knocking out THBS1 can inhibit these abilities of tumor cells. In cardiovascular disease, THBS1 is involved in regulating angiogenesis and inflammatory responses, affecting the development of heart disease.

Bioapplications of THBS1

The use of THBS1 in a variety of diseases suggests that it is an important biomarker and therapeutic target. In nonalcoholic fatty liver disease, THBS1 serves as a novel biomarker, whose elevated serum levels are correlated with liver fat content, and exogenous recombinant THBS1 protein can inhibit liver lipid synthesis induced by high-fat diet in mice, thereby improving fatty liver symptoms. In addition, THBS1 is a potential therapeutic target in the treatment of colorectal cancer. These findings provide new strategies and ideas for the treatment of nonalcoholic fatty liver disease and colorectal cancer.