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Abstract
A disintegrin and metalloprotease like decysin (ADAMDEC1) is a highly conserved secreted metalloprotease that belongs to a family of A disintegrin and metalloprotease (ADAMs). It is expressed exclusively in the gastrointestinal tract of animals and is known to possess a very rare zinc-binding motif (HEXXHXXGXXD) within the metalloprotease domain. The biological function of ADAMDEC1 as well as its true biological substrates remains unknown although its characteristic features reported to date suggest it plays a fundamental role in the physiology of mammals. Historically its expression, in healthy state, was believed to be limited to the monocyte-derived macrophages (MDMs) and dendritic cells within the gastrointestinal tract; however, the recent development of single-cell sequencing has provided evidence supporting its expression in a wider range of cell types. There is an increasing body of evidence linking the alterations in ADAMDEC1 expression and various inflammatory diseases and cancers. Although a detailed mechanistic role of ADAMDEC1 in these conditions remains elusive. In this review, we aim to summarise the characteristic features of this unique metalloprotease, discuss the associations with various human diseases and define the potential mechanistic role of ADAMDEC1 in mammalian physiology.
Abbreviations
ADAMs, A disintegrin and metalloproteases; ADAMDEC1, A disintegrin and metalloprotease like decysin 1; CRC, colorectal cancer; DSS, dextran sodium sulphate; EDAC, epithelial defense against cancer; EGF, epidermal growth factor; RGFR, epidermal growth factor receptor; FGF2, fibroblast growth factor 2; GBM, glioblastoma; GMCSF, granulocyte-macrophage colony-stimulating factor; LOH, loss of heterozygosity; LPS, lipopolysaccharide; MCSF, macrophage colony-stimulating factor; MDCK, Madin-Darby Canine Kidney; MDMs, monocyte-derived macrophages; OA, osteoarthritis; OSCC, oral squamous cell carcinoma; RA, rheumatoid arthritis; SIRT1/2, sirtuins 1 and 2; TIMPs, tissue inhibitors of metalloproteases; TLR2, toll-like receptor 2; WT, wild type; ZEB1, zinc finger E-box-binding homeobox 1.
Acknowledgments
Simone Nunziato kindly created the graphical illustrations and Dr Claire Mulvey (Cancer Research UK Cambridge Institute, University of Cambridge, UK) for critical evaluation of the manuscript.
Author Contributions
All authors contributed to data analysis, drafting or revising the article, have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.
Funding
Tomoko Kumagai was funded by the Medical Research Council (MRC grant code MR/R001901/1).
Disclosure
The authors report no conflicts of interest in this work.