GSDMA deficiency impairs cutaneous squamous cell carcinoma growth

As a member of Gasdermin family, GSDMA is predominantly expressed in epidermal keratinocytes, hair follicle stem cells, and the upper gastrointestinal epithelium. Although it has been reported that GSDMA can be cleaved to trigger pyroptosis, its physiological function remains unclear. In this study, our results uncover a new role of GSDMA in the initiation and progression of cutaneous squamous cell carcinoma (cSCC). Deficiency of Gsdma1/2/3 strongly inhibits cSCC initiation and progression in mice. There is a significant upregulation of Gsdma1 expression in cSCC, but not Gsdma2 or Gsdma3. Mechanistically, we found that deficiency of Gsdma1/2/3 impairs EGFR-AKT axis-mediated cell proliferation during the progression of cSCC. Our findings suggest that GSDMA plays a promoting role in cSCC proliferation and may represent a potential therapeutic target.