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Review
. 2024 Jul 20;14(7):874.
doi: 10.3390/biom14070874.

The Role and Therapeutic Potential of Pyroptosis in Colorectal Cancer: A Review

Qing Fang  1   2 , Yunhua Xu  1   3 , Xiangwen Tan  1   4 , Xiaofeng Wu  1   2 , Shuxiang Li  5 , Jinyi Yuan  5 , Xiguang Chen  5 , Qiulin Huang  5 , Kai Fu  6 , Shuai Xiao  1   5
Affiliations
Review

The Role and Therapeutic Potential of Pyroptosis in Colorectal Cancer: A Review

Qing Fang et al. Biomolecules. .

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. The unlimited proliferation of tumor cells is one of the key features resulting in the malignant development and progression of CRC. Consequently, understanding the potential proliferation and growth molecular mechanisms and developing effective therapeutic strategies have become key in CRC treatment. Pyroptosis is an emerging type of regulated cell death (RCD) that has a significant role in cells proliferation and growth. For the last few years, numerous studies have indicated a close correlation between pyroptosis and the occurrence, progression, and treatment of many malignancies, including CRC. The development of effective therapeutic strategies to inhibit tumor growth and proliferation has become a key area in CRC treatment. Thus, this review mainly summarized the different pyroptosis pathways and mechanisms, the anti-tumor (tumor suppressor) and protective roles of pyroptosis in CRC, and the clinical and prognostic value of pyroptosis in CRC, which may contribute to exploring new therapeutic strategies for CRC.

Keywords: colorectal cancer; growth; proliferation; pyroptosis; therapy.

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Conflict of interest statement

There are no conflicts of interest and disclosures associated with the manuscript.

Figures

Figure 1
Figure 1
The molecular mechanism of pyroptosis. In the caspase-1 mediated canonical inflammasome pathway, after recognition by PRRs, PAMPs form inflammasome complexes. The inflammasome recruits and binds with ASC, activating caspase-1, which induces the formation of perforation-active GSDMD-N. GSDMD-N is released and forms pores in the plasma membrane, leading to secretion of IL-18/1β, influx of water, cell swelling, and rupture, ultimately resulting in pyroptosis. On the other hand, the non-canonical inflammasome pathway of pyroptosis involves recognizing LPS and activating caspase-4/5/11, which cleaves GSDMD to translocate to the cell membrane, triggering pyroptosis. Another novel non-canonical of pyroptosis mediated by caspase-3 is regulated through GSDME. Chemotherapeutic drugs activate caspase-3 to cleave GSDME, leading to widespread pyroptosis. Additionally, in the granzyme-dependent pathway of pyroptosis, GZMB and GZMA can respectively act on GSDME and GSDMB to induce pyroptosis. PAMPs: pathogen-associated molecular patterns; DAMPs: damage-associated molecular patterns; NLRP1: nucleotide-binding domain leucine-rich repeat pyrin domain containing 1; NLRP3: nucleotide-binding domain leucine-rich repeat pyrin domain containing 3; NAIP: NOD-like receptor family apoptosis inhibitory protein; NLRC4: NLR-family CARD-containing protein 4; AIM2: Absent in melanoma 2; ASC: Apoptosis-associated speck like protein containing a CARD; LPS: Lipopolysaccharide.
Figure 2
Figure 2
Signaling pathways of GSDMs in the CRC. GSDM proteins can regulate cell proliferation and differentiation and also serve as effector proteins in pyroptosis, triggering inflammation and cell death. Various stimuli and upstream signals such as lobaplatin, RT, 5-aza-dC, apoptin, and GA can induce GSDME cleavage and subsequent cell death. Caspase-1/GSDMD-dependent pyroptosis is induced by activating molecules, including SDG, FOXP2, GRh3, and CLNA1. CLNA2 induces cell pyroptosis through the activation of caspase-4/5. GSDMB and GSDMC participate in pyroptosis and subsequent cell death through the GZMA and TGFBR2, respectively. 5-aza-dC: 5-aza-2′-deoxycytidine; RT: radiation therapy; GA: gambogic acid; DSS: dextran sulfate sodium; GRh3: ginsenoside Rh3.
Figure 3
Figure 3
Prospects of pyroptosis in CRC treatment. The use of chemotherapy drugs, RT, immunotherapy, and targeted pyroptosis can effectively induce CRC cells pyroptosis, thereby improving the treatment effect.
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References

    1. Siegel R.L., Miller K.D., Wagle N.S., Jemal A. Cancer statistics, 2023. CA Cancer J. Clin. 2023;73:17–48. doi: 10.3322/caac.21763. - DOI - PubMed
    1. Zheng R., Zhang S., Zeng H., Wang S., Sun K., Chen R., Li L., Wei W., He J. Cancer incidence and mortality in China, 2016. J. Natl. Cancer Cent. 2022;2:1–9. doi: 10.1016/j.jncc.2022.02.002. - DOI - PMC - PubMed
    1. Wan M.L., Wang Y., Zeng Z., Deng B., Zhu B.S., Cao T., Li Y.K., Xiao J., Han Q., Wu Q. Colorectal cancer (CRC) as a multifactorial disease and its causal correlations with multiple signaling pathways. Biosci. Rep. 2020;40:BSR20200265. doi: 10.1042/BSR20200265. - DOI - PMC - PubMed
    1. Brody H. Colorectal cancer. Nature. 2015;521:S1. doi: 10.1038/521S1a. - DOI - PubMed
    1. Dekker E., Tanis P.J., Vleugels J.L.A., Kasi P.M., Wallace M.B. Colorectal cancer. Lancet. 2019;394:1467–1480. doi: 10.1016/S0140-6736(19)32319-0. - DOI - PubMed

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