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ADAM17 and its proteolytic targets in disease pathogenesis

Abdulbasit Amin1,2, Marina Badenes3,4,5

  • 1Gulbenkian Institute for Molecular Medicine (GIMM), Lisbon, Portugal.

The FEBS Journal
|March 23, 2026
PubMed

Insights

ADAM17, a protease regulating growth and inflammation, is a key target for treating cancer and inflammatory diseases. Its role extends to cardiovascular and metabolic conditions, highlighting its broad therapeutic potential.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pathophysiology

Background:

  • ADAM17, also known as TACE, is a metalloproteinase with over 90 substrates.
  • It regulates critical signaling pathways, including EGFR and TNF, impacting cell growth and inflammation.
  • ADAM17 is implicated in various diseases, making it a significant therapeutic target.

Purpose of the Study:

  • To review the current understanding of ADAM17.
  • To summarize the involvement of ADAM17 targets in major disease categories.
  • To highlight ADAM17's role in inflammation, cancer, and cardiovascular/metabolic diseases.

Main Methods:

  • Literature review of scientific publications.
  • Analysis of ADAM17's enzymatic activity and substrate interactions.
  • Synthesis of data on ADAM17's role in disease pathogenesis.

Main Results:

  • ADAM17 is a pleiotropic protease crucial for EGFR and TNF signaling.
  • Its substrates are involved in fundamental biological processes like growth and inflammation.
  • ADAM17 dysregulation is linked to cancer, inflammatory, cardiovascular, and metabolic diseases.

Conclusions:

  • ADAM17 is a central regulator in multiple signaling networks.
  • Targeting ADAM17 offers therapeutic potential for diverse pathological conditions.
  • Further research into ADAM17 biology can uncover novel treatment strategies.
Keywords:
ADAM17cancercardiovascular diseasesinflammationmetabolic diseases

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