4.6 Review

Insulin-Degrading Enzyme, an Under-Estimated Potential Target to Treat Cancer?

Journal

CELLS
Volume 11, Issue 7, Pages -

Publisher

MDPI
DOI: 10.3390/cells11071228

Keywords

insulin-degrading enzyme; cancer; target

Categories

Funding

  1. INSERM PCSI [ASC20017ESA]
  2. Agence Nationale de la Recherche [ANR-10-LABX-0046]
  3. Hauts-de-France Regional Council [17003781]
  4. Metropole Europeenne de Lille [2016_ESR_05]
  5. FEDER [20000007]
  6. [2017-R3-CTRL-Phase 1]

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Insulin-degrading enzyme (IDE) is a multifunctional protease that has been implicated in metabolic and neuronal diseases. Recent studies have also shown IDE's overexpression in different cancers, suggesting its potential as a target in cancer therapeutics. Further research is needed to fully understand IDE's role in cancer development, but pharmacological modulation of IDE has shown promising results in cancer models.
Insulin-degrading enzyme (IDE) is a multifunctional protease due to the variety of its substrates, its various cellular locations, its conservation between species and its many non-proteolytic functions. Numerous studies have successfully demonstrated its implication in two main therapeutic areas: metabolic and neuronal diseases. In recent years, several reports have underlined the overexpression of this enzyme in different cancers. Still, the exact role of IDE in the physiopathology of cancer remains to be elucidated. Known as the main enzyme responsible for the degradation of insulin, an essential growth factor for healthy cells and cancer cells, IDE has also been shown to behave like a chaperone and interact with the proteasome. The pharmacological modulation of IDE (siRNA, chemical compounds, etc.) has demonstrated interesting results in cancer models. All these results point towards IDE as a potential target in cancer. In this review, we will discuss evidence of links between IDE and cancer development or resistance, IDE's functions, catalytic or non-catalytic, in the context of cell proliferation, cancer development and the impact of the pharmacomodulation of IDE via cancer therapeutics.

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