ADAM17 and its proteolytic targets in disease pathogenesis.

ADAM17, from the disintegrin and metalloproteinase (ADAM) family, also called tumor necrosis factor converting enzyme (TACE), is a pleiotropic protease with more than 90 substrates, including growth factors, cytokines, receptors, and adhesion molecules. The biology of ADAM17 has been extensively studied, mainly as a regulator of epidermal growth factor receptor (EGFR) and tumor necrosis factor (TNF) signaling pathways, which are crucial for growth and inflammation, respectively. Consequently, this protease has been considered a major target to treat human cancers and inflammatory disorders. Moreover, it is involved in the pathobiology of numerous other disease types. This review summarizes the current understanding of ADAM17 and the involvement of its targets in inflammation, cancer, and cardiovascular and metabolic diseases.