Skip to main content
Erschienen in: Archivum Immunologiae et Therapiae Experimentalis 1/2023

01.12.2023 | Review

The Pyroptotic and Nonpyroptotic Roles of Gasdermins in Modulating Cancer Progression and Their Perspectives on Cancer Therapeutics

verfasst von: Sheng-Kai Hsu, Yi-En Chen, En-De Shu, Ching-Chung Ko, Wen-Tsan Chang, I.-Ling Lin, Chia-Yang Li, Rovelyn P. Gallego, Chien-Chih Chiu

Erschienen in: Archivum Immunologiae et Therapiae Experimentalis | Ausgabe 1/2023

Einloggen, um Zugang zu erhalten

Abstract

Gasdermins (GSDMs) are a protein family encoded by six paralogous genes in humans, including GSDMA, GSDMB, GSDMC, GSDMD, GSDME (also known as DFNA5), and DFNB59 (also known as pejvakin). Structurally, members of the GSDM family possess a C-terminus (an autoinhibitory domain) and a positively charged N-terminus (a pore-forming domain) linked with divergent peptide linkers. Recently, GSDMs have been identified as key executors of pyroptosis (an immunogenic programmed cell death) due to their pore-forming activities on the plasma membrane when proteolytically cleaved by caspases or serine proteases. Accumulating studies suggest that chemoresistance is attributed to dysregulation of apoptotic machinery and that inducing pyroptosis to bypass aberrant apoptosis can potently resensitize apoptosis-resistant cancer to chemotherapeutics. Pyroptosis is initiated by pore formation and culminates with plasma membrane rupture; these processes enable the release of proinflammatory cytokines (e.g., IL-1β and IL-18) and damage-associated molecular patterns, which further modulate antitumor immunity within the tumor microenvironment. Although pyroptosis is considered a promising strategy to boost antitumor effects, it is also reported to cause unwanted tissue damage (e.g., gut damage and nephrotoxicity). Intriguingly, mounting evidence has uncovered nonpyroptotic roles of GSDMs in tumorigenesis, such as proliferation, invasion, metastasis, and drug resistance. Thus, this provides a rationale for GSDMs as potential therapeutic targets. Taken together, we shed unbiased light on the pyroptosis-dependent roles of GSDMs in cancer progression and highlighted how GSDMs modulate tumorigenesis in a pyroptosis-independent manner. It is evident that targeting GSDMs seems profound in cancer management; however, several problems require further investigation to target GSDMs from bench to bedside, which is elucidated in the discussion section.
Literatur
Zurück zum Zitat Zhong N, Yu Y, Pan G et al (2021b) Effect of GSDMB polymorphism on sensitivity to chemoradiation therapy for cervical cancer. Clin Exp Obstetrics Gynecol 48:1374–1380CrossRef Zhong N, Yu Y, Pan G et al (2021b) Effect of GSDMB polymorphism on sensitivity to chemoradiation therapy for cervical cancer. Clin Exp Obstetrics Gynecol 48:1374–1380CrossRef
Metadaten
Titel
The Pyroptotic and Nonpyroptotic Roles of Gasdermins in Modulating Cancer Progression and Their Perspectives on Cancer Therapeutics
verfasst von
Sheng-Kai Hsu
Yi-En Chen
En-De Shu
Ching-Chung Ko
Wen-Tsan Chang
I.-Ling Lin
Chia-Yang Li
Rovelyn P. Gallego
Chien-Chih Chiu
Publikationsdatum
01.12.2023
Verlag
Springer International Publishing
Erschienen in
Archivum Immunologiae et Therapiae Experimentalis / Ausgabe 1/2023
Print ISSN: 0004-069X
Elektronische ISSN: 1661-4917
DOI
https://doi.org/10.1007/s00005-023-00678-9

Weitere Artikel der Ausgabe 1/2023

Archivum Immunologiae et Therapiae Experimentalis 1/2023 Zur Ausgabe