Molecular mechanism of pyroptosis and its relationship with malignant tumors / 中国肿瘤临床

ABSTRACT

Pyroptosis is a form of programmed cell death, and can be mediated by caspase-1, caspase-3, caspase-4, caspase-5, caspase-8, and caspase-11. It is primarily induced through two pathways in which inflammasomes play an important role the canonical and non-canonical pathways. Gasdermin D is a critical substrate for pyroptosis. Following enzymatic cleavage, gasdermin D releases N-terminal fragments that generate pores on the plasma membrane. This causes osmotic lysis and ultimately, the release of cytosolic content which consequently induces inflammatory responses. Various intermediaries of the pyroptotic cell death pathways are involved in cancer initiation, invasion and metastasis; hence, the research on pyroptosis exploits a new field of cancer treatment. In this review, we summarize the recent progresses in research focused on elucidating the molecular mechanism of pyroptosis, discovering the effects of pyroptotic-related molecules on the initiation and progression of cancer, and the applications and prospects of targeting pyroptosis for cancer treatments based specifically on the development of chemotherapy drugs.