INSERM U1177 Drugs and Molecules for Living Systems, Institut Pasteur de Lille, European Genomic Institute for Diabetes, University of Lille, F-59000 Lille, France.
Cells. 2022 Apr 5;11(7):1228. doi: 10.3390/cells11071228.
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.
胰岛素降解酶（IDE）是一种多功能蛋白酶，这归因于其底物的多样性、其各种细胞位置、物种间的保守性以及其许多非蛋白水解功能。大量研究成功证明了它在两个主要治疗领域的作用：代谢和神经疾病。近年来，有几项报告强调了这种酶在不同癌症中的过度表达。然而，IDE 在癌症病理生理学中的确切作用仍有待阐明。作为主要负责降解胰岛素的酶，胰岛素是健康细胞和癌细胞的必需生长因子，IDE 也被证明具有伴侣蛋白的作用，并与蛋白酶体相互作用。IDE 的药理学调节（siRNA、化学化合物等）在癌症模型中显示出了有趣的结果。所有这些结果都表明 IDE 是癌症的一个潜在靶点。在这篇综述中，我们将讨论 IDE 与癌症发展或耐药性之间的联系的证据，以及在细胞增殖、癌症发展以及通过癌症治疗药物对 IDE 的药理学调节的影响的背景下，IDE 的催化或非催化功能。
