Skip to Main content Skip to Navigation
Journal articles

Epigenetic Regulation of TRAIL Signaling: Implication for Cancer Therapy

Abstract : One of the main characteristics of carcinogenesis relies on genetic alterations in DNA and epigenetic changes in histone and non-histone proteins. At the chromatin level, gene expression is tightly controlled by DNA methyl transferases, histone acetyltransferases (HATs), histone deacetylases (HDACs), and acetyl-binding proteins. In particular, the expression level and function of several tumor suppressor genes, or oncogenes such as c-Myc, p53 or TRAIL, have been found to be regulated by acetylation. For example, HATs are a group of enzymes, which are responsible for the acetylation of histone proteins, resulting in chromatin relaxation and transcriptional activation, whereas HDACs by deacetylating histones lead to chromatin compaction and the subsequent transcriptional repression of tumor suppressor genes. Direct acetylation of suppressor genes or oncogenes can affect their stability or function. Histone deacetylase inhibitors (HDACi) have thus been developed as a promising therapeutic target in oncology. While these inhibitors display anticancer properties in preclinical models, and despite the fact that some of them have been approved by the FDA, HDACi still have limited therapeutic efficacy in clinical terms. Nonetheless, combined with a wide range of structurally and functionally diverse chemical compounds or immune therapies, HDACi have been reported to work in synergy to induce tumor regression. In this review, the role of HDACs in cancer etiology and recent advances in the development of HDACi will be presented and put into perspective as potential drugs synergizing with TRAIL's pro-apoptotic potential.
Document type :
Journal articles
Complete list of metadata

Cited literature [236 references]  Display  Hide  Download
Contributor : Olivier Micheau Connect in order to contact the contributor
Submitted on : Wednesday, June 3, 2020 - 3:30:45 PM
Last modification on : Thursday, September 1, 2022 - 11:05:52 AM
Long-term archiving on: : Thursday, December 3, 2020 - 7:06:15 AM


Publisher files allowed on an open archive



Mohammed Elmallah, Olivier Micheau. Epigenetic Regulation of TRAIL Signaling: Implication for Cancer Therapy. Cancers, MDPI, 2019, 11 (6), pp.850. ⟨10.3390/cancers11060850⟩. ⟨inserm-02749483⟩



Record views


Files downloads