Publications by authors named "Elke De Schutter"

2 Publications

  • Page 1 of 1

Punching Holes in Cellular Membranes: Biology and Evolution of Gasdermins.

Trends Cell Biol 2021 Mar 23. Epub 2021 Mar 23.

Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium; Methusalem program Cell Death Activity Regulation in Inflammation and Cancer (CEDAR-IC), Ghent University, Ghent, Belgium. Electronic address:

The gasdermin (GSDM) family has evolved as six gene clusters (GSDMA-E and Pejvakin, PJVK), and GSDM proteins are characterized by a unique N-terminal domain (N-GSDM). With the exception of PJVK, the N-GSDM domain is capable of executing plasma membrane permeabilization. Depending on the cell death modality, several protease- and kinase-dependent mechanisms directly regulate the activity of GSDME and GSDMD, the two most widely expressed and best-studied GSDMs. We provide an overview of all GSDMs in terms of biological function, tissue expression, activation, regulation, and structure. In-depth phylogenetic analysis reveals that GSDM genes show many gene duplications and deletions, suggesting that strong evolutionary forces and a unique position of the PJVK gene are associated with the occurrence of complex inner-ear development in vertebrates.
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http://dx.doi.org/10.1016/j.tcb.2021.03.004DOI Listing
March 2021

GSDME and its role in cancer: From behind the scenes to the front of the stage.

Int J Cancer 2020 Nov 13. Epub 2020 Nov 13.

Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Antwerp, Belgium.

Gasdermin E (GSDME), a gene originally involved in hereditary hearing loss, has been associated with several types of cancer in the last two decades. Recently, GSDME was identified as a pore-forming molecule, which is activated following caspase-3-mediated cleavage resulting in so-called secondary necrosis following apoptotic cell death, or in primary necrotic cell death without an apoptotic phase, so-called pyroptosis-like. This implication in cell death execution suggests its potential role as a tumor suppressor. GSDME also exhibited a cancer type-specific differential methylation pattern between tumor tissues and normal cells, implying GSDME gene methylation as both a pan-cancer and cancer type-specific detection biomarker. A bit paradoxically, GSDME protein expression is considered to be less suited as biomarker, and although its ablation does not protect the cell against eventual cell death, its protein expression might still operate in tumor immunogenicity due to its capacity to induce (secondary) necrotic cell death, which has enhanced immunogenic properties. Additionally, GSDME gene expression has been shown to be associated with favorable prognosis following chemotherapy, and it could therefore be a potential predictive biomarker. We provide an overview of the different associations between GSDME gene methylation, gene expression and tumorigenesis, and explore their potential use in the clinic. Our review only focuses on GSDME and summarizes the current knowledge and most recent advances on GSDME's role in cancer formation, its potential as a biomarker in cancer and on its promising role in immunotherapies and antitumor immune response.
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http://dx.doi.org/10.1002/ijc.33390DOI Listing
November 2020