The metalloprotease ADAM17 in inflammation and cancer

Stefan Düsterhöft; Juliane Lokau; Christoph Garbers

doi:10.1016/j.prp.2019.04.002

The metalloprotease ADAM17 in inflammation and cancer

Pathol Res Pract. 2019 Jun;215(6):152410. doi: 10.1016/j.prp.2019.04.002. Epub 2019 Apr 6.

Authors

Stefan Düsterhöft¹, Juliane Lokau², Christoph Garbers³

Affiliations

¹ Institute for Pharmacology and Toxicology, RWTH Aachen University, Aachen, Germany.
² Department of Pathology, Otto-von-Guericke-University Magdeburg, Medical Faculty, Magdeburg, Germany.
³ Department of Pathology, Otto-von-Guericke-University Magdeburg, Medical Faculty, Magdeburg, Germany. Electronic address: christoph.garbers@med.ovgu.de.

PMID: 30992230
DOI: 10.1016/j.prp.2019.04.002

Abstract

Proteolytic cleavage of transmembrane proteins is an important post-translational modification that regulates the biological function of numerous transmembrane proteins. Among the 560 proteases encoded in the human genome, the metalloprotease A Disintegrin and Metalloprotease 17 (ADAM17) has gained much attention in recent years and has emerged as a central regulatory hub in inflammation, immunity and cancer development. In order to do so, ADAM17 cleaves a variety of substrates, among them the interleukin-6 receptor (IL-6R), the pro-inflammatory cytokine tumor necrosis factor α (TNFα) and most ligands of the epidermal growth factor receptor (EGFR). This review article provides an overview of the functions of ADAM17 with a special focus on its cellular regulation. It highlights the importance of ADAM17 to understand the biology of IL-6 and TNFα and their role in inflammatory diseases. Finally, the role of ADAM17 in the formation and progression of different tumor entities is discussed.

Keywords: ADAM17; Cancer; IL-6; Inflammation; Proteolysis; TNFα.

Publication types

Review

MeSH terms

ADAM17 Protein / metabolism*
Animals
Humans
Inflammation / enzymology*
Neoplasms / enzymology*

Substances

ADAM17 Protein