A disintegrin and metalloproteinase with thrombospondin motifs 18 (ADAMTS18)

A disintegrin and metalloproteinase with thrombospondin motifs 18 (ADAMTS18) is a secreted zinc-dependent metalloproteinase and a member of the ADAMTS family, which are known for their roles in extracellular matrix (ECM) remodeling through proteolytic activity. ADAMTS18 is highly modular, containing a signal peptide, pro-domain, catalytic metalloprotease domain, disintegrin-like domain, multiple thrombospondin type 1 repeats, a cysteine-rich region, and a unique C-terminal PLAC domain. It is expressed in various adult and fetal tissues and plays critical roles in ECM dynamics, affecting cell proliferation, migration, invasion, apoptosis, and tissue fibrosis. In cancer biology, ADAMTS18 frequently has tumor-suppressive roles, often silenced by promoter methylation, but may act as a tumor promoter in some cancers. It regulates mechanosignaling in the tumor microenvironment by cleaving substrates such as fibronectin and fibrillin-1. Additionally, ADAMTS18 can activate latent TGF-β, contributing to tissue fibrosis. Despite being a candidate therapeutic target, there are no approved drugs directly targeting ADAMTS18, but it modulates response to drugs such as cisplatin, sunitinib, axitinib, and curcumin by influencing cellular signaling pathways and sensitivity.

Other names

ADAM metallopeptidase with thrombospondin type 1 motif 18ADAMTS-18ADAM-TS 18ADAM-TS18KNO2MMCATdisintegrin and metalloprotease-like proteina disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 18a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 21ADAMTS21 (note: ADAMTS18 and ADAMTS21 are separate genes, their conflation in some aliases is incorrect)

Enhanced drug sensitivity (cisplatin, sunitinib, axitinib, curcumin) by modulating cellular proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) pathways (e.g., through inhibition or activation of EGFR/AKT, ERK, and NF-κB pathways).