Gasdermin E mediates pyroptosis in the progression of hepatocellular carcinoma: a double-edged sword

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer worldwide. It usually develops due to viral hepatitis or liver cirrhosis. The molecular mechanisms involved in HCC pathogenesis are complex and incompletely understood. Gasdermin E (GSDME) is a tumor suppressor gene and is inhibited in most cancers. Recent studies have reported that, unlike those in most tumors, GSDME is highly expressed in liver cancer, and GSDME expression in HCC is negatively associated with prognosis, suggesting that GSDME may promote HCC. However, antitumor drugs can induce pyroptosis through GSDME, killing HCC cells. Therefore, GSDME may both inhibit and promote HCC development. Because functional studies of GSDME in HCC are limited, the precise molecular mechanisms of GSDME in liver cancer remain unclear. In this article, we have reviewed the role, related mechanisms, and clinical importance of GSDME at the onset and development of HCC to provide a theoretical foundation to improve the clinical diagnosis and treatment of liver cancer.