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. 2020;24(8):291-299.
doi: 10.4267/2042/70774.

THBS1 (thrombospondin-1)

Jeffrey S Isenberg  1 , David D Roberts  2
Affiliations

THBS1 (thrombospondin-1)

Jeffrey S Isenberg et al. Atlas Genet Cytogenet Oncol Haematol. 2020.

Abstract

Thrombospondins are encoded in vertebrates by a family of 5 THBS genes. THBS1 is infrequently mutated in most cancers, but its expression is positively regulated by several tumor suppressor genes and negatively regulated by activated oncogenes and promoter hypermethylation. Consequently, thrombospondin-1 expression is frequently lost during oncogenesis and is correlated with a poor prognosis for some cancers. Thrombospondin-1 is a secreted protein that acts in the tumor microenvironment to inhibit angiogenesis, regulate antitumor immunity, stimulate tumor cell migration, and regulate the activities of extracellular proteases and growth factors. Differential effects of thrombospondin-1 on the sensitivity of normal versus malignant cells to ischemic and genotoxic stress also regulate the responses to tumors to therapeutic radiation and chemotherapy.

Keywords: matricellular; metastasis; resistance to genotoxic therapy; thrombospondin-1; tumor angiogenesis.

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Figures

Figure 1.
Figure 1.
Exon/intron organization of the THBS1 gene.
Figure 2.
Figure 2.
Domain organization and localization of selected ligand binding sites in THBS1. THBS1 is a homotrimer linked via disulfide bonds.
Figure 3.
Figure 3.
Identified mutations in thrombospondin-1 in human cancers include 187 missense (green), 41 truncating nonsense (black), 3 in frame (brown), and 2 other (purple). Data is from The Cancer Genome Atlas (TCGA) using cBioPortal tools to analyze data from 10,953 patients.
Figure 4.
Figure 4.
Frequency of THBS1 mutations in TCGA PanCancer data classified by cancer type using cBioPortal tools (green = mutation, purple= fusion, blue= deletion, red = amplification, grey= multiple alterations).
See this image and copyright information in PMC

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