A Disintegrin and Metalloproteinase-12 (ADAM12): Function, Roles in Disease Progression, and Clinical Implications

Overview

Journal Biochim Biophys Acta

Specialties Biochemistry
Biophysics

Date 2013 May 18

PMID 23680494

Citations 28

Authors

Erin K Nyren-Erickson

Justin M Jones

D K Srivastava

Sanku Mallik

Affiliations

Soon will be listed here.

Abstract

Background: A disintegrin and metalloproteinase-12 (ADAM12) is a member of the greater ADAM family of enzymes: these are multifunctional, generally membrane-bound, zinc proteases for which there are forty genes known (21 of these appearing in humans). ADAM12 has been implicated in the pathogenesis of various cancers, liver fibrogenesis, hypertension, and asthma, and its elevation or decrease in human serum has been linked to these and other physiological/pathological conditions.

Scope: In this review, we begin with a brief overview of the ADAM family of enzymes and protein structure. We then discuss the role of ADAM12 in the progression and/or diagnosis of various disease conditions, and we will conclude with an exploration of currently known natural and synthetic inhibitors.

Major Conclusion: ADAM12 has potential to emerge as a successful drug target, although targeting the metalloproteinase domain with any specificity will be difficult to achieve due to structural similarity between the members of the ADAM and MMP family of enzymes. Overall, more research is required to establish ADAM12 being as a highly desirable biomarker and drug target of different diseases, and their selective inhibitors as potential therapeutic agents.

General Significance: Given the appearance of elevated levels of ADAM12 in various diseases, particularly breast cancer, our understanding of this enzyme both as a biomarker and a potential drug target could help make significant inroads into both early diagnosis and treatment of disease.

Citing Articles

A disintegrin and metallopeptidase domain (ADAM) 12, ADAM 17 mRNA and ADAM10 protein hold potential as biomarkers for detection of early gastric cancer.

Oh S, Lee S, Jin H, Choi S, Cha C, Lee J Sci Rep. 2025; 15(1):763.

PMID: 39755747 PMC: 11700123. DOI: 10.1038/s41598-024-84237-y.

A disintegrin and metalloprotease 12 contributes to colorectal cancer metastasis by regulating epithelial‑mesenchymal transition.

Oh H, Park Y, Park S, Joo Y Int J Oncol. 2023; 62(4).

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The Canine Pancreatic Extracellular Matrix in Diabetes Mellitus and Pancreatitis: Its Essential Role and Therapeutic Perspective.

Pantoja B, Carvalho R, Miglino M, Carreira A Animals (Basel). 2023; 13(4).

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Alternatively Spliced Isoforms of and as Biomarkers for Colorectal Cancer Metastasis.

Althenayyan S, AlMuhanna M, AlAbdulrahman A, Alghanem B, Alsagaby S, Alfahed A J Pers Med. 2023; 13(1).

PMID: 36675796 PMC: 9861497. DOI: 10.3390/jpm13010135.

ADAM12 abrogation alters immune cell infiltration and improves response to checkpoint blockade therapy in the T11 murine model of triple-negative breast cancer.

Wang G, Romero Y, Thevarajan I, Zolkiewska A Oncoimmunology. 2022; 12(1):2158006.

PMID: 36545255 PMC: 9762783. DOI: 10.1080/2162402X.2022.2158006.

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