4.8 Review

Pyroptosis in inflammatory diseases and cancer

Journal

THERANOSTICS
Volume 12, Issue 9, Pages 4310-4329

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/thno.71086

Keywords

Pyroptosis; signaling pathway; gasdermin; inflammatory diseases; cancer

Funding

  1. National Key Research and Development Program of China [2017YFC1309100, 2017YFA0205200]
  2. National Natural Science Foundation of China [21804104, 91959124, 81671753, 32101147, 32071406]
  3. Innovation Capability Support Program of Shaanxi [S2022-ZC-TD-0125]
  4. Natural Science Foundation of Shaanxi Province of China [S2020-ZC-PT-0010]
  5. Youth Innovation Team of Shaanxi Universities
  6. Natural Science Basic Research Plan in Shaanxi Province of China [2021JM-147, 2021JQ-212]
  7. Fundamental Research Funds for the Central Universities [JB211201, JB211202, JB211204]

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Pyroptosis is a critical type of programmed cell death that plays a key role in host defense against pathogen infection and can serve as a new strategy for cancer elimination. Excessive pyroptosis, however, may lead to inflammatory diseases. Therefore, it is important to fully understand the molecular mechanisms and therapeutic implications of pyroptosis.
Pyroptosis is a lytic and inflammatory type of programmed cell death that is usually triggered by inflammasomes and executed by gasdermin proteins. The main characteristics of pyroptosis are cell swelling, membrane perforation, and the release of cell contents. In normal physiology, pyroptosis plays a critical role in host defense against pathogen infection. However, excessive pyroptosis may cause immoderate and continuous inflammatory responses that involves in the occurrence of inflammatory diseases. Attractively, as immunogenic cell death, pyroptosis can serve as a new strategy for cancer elimination by inducing pyroptotic cell death and activating intensely antitumor immunity. To make good use of this double-edged sword, the molecular mechanisms, and therapeutic implications of pyroptosis in related diseases need to be fully elucidated. In this review, we first systematically summarize the signaling pathways of pyroptosis and then present the available evidences indicating the role of pyroptosis in inflammatory diseases and cancer. Based on this, we focus on the recent progress in strategies that inhibit pyroptosis for treatment of inflammatory diseases, and those that induce pyroptosis for cancer therapy. Overall, this should shed light on future directions and provide novel ideas for using pyroptosis as a powerful tool to fight inflammatory diseases and cancer.

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