Expression and prognosis of ADAMTS18 in different tumors

Abstract

ADAMTS18 has been identified as an orphan member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of Zn-dependent secreted metalloproteinases since 2002. Despite the recent breakthroughs in tumor biology of ADAMTS18, there is no literature systematically discussing the relationship between ADAMTS18 and cancer. In this review, we will summarize the expression pattern and prognostic value of ADAMTS18 in various cancers. In addition, we will highlight the biological functions of ADAMTS18 in the tumor microenvironment, including the regulation of cell proliferation signals, death patterns, invasion, and migration, which influence cancer progression.

Keywords: ADAMTS18; invasion; migration; prognosis; tumor microenvironment.

Figure 1

The domain organization of ADAMTS18.

Figure 2

Signal pathway including ADAMTS18 related to cancer. Wnt/β-catenin signal pathway: ADAMTS18 prevents the transfer of β-catenin from the cytoplasm to the nucleus and binds to transcription factors, hindering the transcription of downstream target genes CCND1 and C-MYC, and the growth of cancer cells is inhibited. PI3K/AKT/NF-κB signal pathway: ADAMTS18 inhibits the PI3K/AKT/NF-κB signal pathway, inhibiting cancer cell migration and invasion by EMT. On the other hand, ADAMTS18, as an antagonist of EGFR, also inhibits AKT signal transduction. MAPK signal pathway: ADAMTS18 promotes apoptosis, inhibits inflammation, and exhibits anti-tumorigenic by inhibiting the ERK/P38 MAPK signal pathway. ADAMTS18 is shown to down-regulate the expression of NCOA4 and FTH1 protein levels and induce ferroptosis in cancer cells. In addition, the ERK signal pathway also promotes EMT. ADAMTS18 inhibits cell secretion of MMP9 and FN by inhibiting JNK signal pathway activity and reducing LOXL2 protein level.