An Overview of ADAM9: Structure, Activation, and Regulation in Human Diseases

Int J Mol Sci. 2020 Oct 21;21(20):7790. doi: 10.3390/ijms21207790.

Abstract

ADAM9 (A disintegrin and a metalloprotease 9) is a membrane-anchored protein that participates in a variety of physiological functions, primarily through the disintegrin domain for adhesion and the metalloprotease domain for ectodomain shedding of a wide variety of cell surface proteins. ADAM9 influences the developmental process, inflammation, and degenerative diseases. Recently, increasing evidence has shown that ADAM9 plays an important role in tumor biology. Overexpression of ADAM9 has been found in several cancer types and is correlated with tumor aggressiveness and poor prognosis. In addition, through either proteolytic or non-proteolytic pathways, ADAM9 promotes tumor progression, therapeutic resistance, and metastasis of cancers. Therefore, comprehensively understanding the mechanism of ADAM9 is crucial for the development of therapeutic anti-cancer strategies. In this review, we summarize the current understanding of ADAM9 in biological function, pathophysiological diseases, and various cancers. Recent advances in therapeutic strategies using ADAM9-related pathways are presented as well.

Keywords: ADAM9; biological function; cancer; inflammation.

Publication types

  • Review

MeSH terms

  • ADAM Proteins / antagonists & inhibitors
  • ADAM Proteins / chemistry*
  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Neoplasms / therapy
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology*
  • Phenylurea Compounds / pharmacology
  • Pyridines / pharmacology
  • Retinal Diseases / metabolism
  • Retinal Diseases / pathology*
  • Sorafenib / pharmacology
  • Tumor Microenvironment

Substances

  • Membrane Proteins
  • Phenylurea Compounds
  • Pyridines
  • regorafenib
  • Sorafenib
  • ADAM Proteins
  • ADAM9 protein, human