Molecular mechanism of pyroptosis and its role in cancer

Pyroptosis is a newly discovered form of cell death that occurs when pathogen-associated molecular patterns or endogenous danger signals are recognized by cells. In response to these signals, human caspase-1/4/5 or murine caspase-11 are activated and cleave Gasdermin D, leading to the formation of cell membrane pores, release of inflammatory factors, and eventually cell death. Gasdermin D is the sole executor of pyroptosis, which is therefore defined as an inflammatory form of programmed cell death mediated by Gasdermin D. Earlier studies on pyroptosis shed light on the roles of pyroptosis and its related proteins involved in mediating the body’s defense against infection. Accumulating evidence suggests that pyroptosis, in addition to inflammatory factors, also plays a pivotal role in cancer development and progression. This article reviews the evolution and development of the concept of pyroptosis from a historical perspective and summarizes the role of the Gasdermin family of proteins in modulating pyroptosis. In addition, it details the emerging evidence that pyroptosis, its related proteins, and inflammatory factors may be drivers of diseases, particularly cancer.