Molecular mechanisms and therapeutic relevance of gasdermin E in human diseases

Gasdermin E (GSDME) is one of the main members of the GSDM family and is originally involved in hereditary hearing loss. Recent studies have reported that GSDME expression is epigenetically silenced by methylation in several common tumours, thereby enhancing tumour proliferation and metastasis. GSDME is also downregulated in cancer tissues compared with normal tissues, which suggests that GSDME can be considered a tumour suppressor. Furthermore, GSDME is the effector protein of caspase-3 and granzyme B in pyroptosis, and it plays a significant role in innate immunity, tissue damage, cancer, and hearing loss, thus revealing potential novel therapeutic avenues. A great deal of evidence reveals that GSDME can be implemented as a biomarker in cancer diagnosis and monitoring, chemotherapy, immunotherapy, and chemoresistance. Based on the current knowledge of GSDME, this review is focussed on its mechanism of action and the most recent advances in its role in cancer and normal physiology.