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The role of pyroptosis in hepatocellular carcinoma

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Abstract

Hepatocellular carcinoma (HCC) is the main histologic type of liver cancer. It accounts for the majority of all diagnoses and deaths due to liver cancer. The induction of tumor cell death is an effective strategy to control tumor development. Pyroptosis is an inflammatory programmed cell death caused by microbial infection, accompanied by activation of inflammasomes and release of pro-inflammatory cytokines, interleukin-1β (IL-1β), and interleukin-18 (IL-18). The cleavage of gasdermins (GSDMs) promotes the occurrence of pyroptosis leading to cell swelling, lysis, and death. Accumulating evidence has indicated that pyroptosis influences the progression of HCC by regulating immune-mediated tumor cell death. Currently, some researchers hold the view that inhibition of pyroptosis-related components may prevent the incidence of HCC, but more researchers have the view that activation of pyroptosis exerts a tumor-inhibitory effect. Growing evidence indicates that pyroptosis can prevent or promote tumor development depending on the type of tumor. In this review, pyroptosis pathways and pyroptosis-related components were discussed. Next, the role of pyroptosis and its components in HCC was described. Finally, the therapeutic significance of pyroptosis in HCC was discussed.

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Abbreviations

AFP:

Alpha-fetoprotein

AIM2:

absent in melanoma 2

ALD:

alcohol-related liver disease

ALR:

AIM2-like receptor

As2O3 :

Arsenic trioxide

ASC:

apoptosis-associated speck-like protein containing a CARD

DAMPs:

damage-associated molecular patterns

DILI:

drug-induced liver injury

dsDN:

double-stranded DNA

E2:

17β-estradiol

GSDMB:

Gasdermin B

GSDMC:

Gasdermin C

GSDMD:

Gasdermin D

GSDMD-N:

the N-terminus of GSDMD

GSDME:

Gasdermin E

GZMA:

granzyme A

HCC:

Hepatocellular carcinoma

HMGB1:

high-mobility group box 1

I/R:

ischemic reperfusion

LDH:

lactate dehydrogenase

LPS:

lipopolysaccharide

MAPKs:

mitogen-activated protein kinases

NAFLD:

nonalcoholic fatty liver disease

NASH:

non-alcoholic steatohepatitis

NF-κB:

nuclear factor kappa-light-chain-enhancer of activated B cells

NLRC4:

NOD-like receptor containing CARD 4

NLRP:

NLR family pyrin domain-containing

NLRP3:

NLR family pyrin domain-containing 3

NLRs:

NOD-like receptors

NOD:

nucleotide-binding oligomerization domain

PAMPs:

pathogen-associated molecular patterns

PD-L1:

programmed cell death protein ligand-1

PRRs:

pattern recognition receptors

RAGE:

receptor for advanced glycation end products

sRNA:

double-stranded RNA

TLRs:

toll-like receptors

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This review was funded by the National Natural Science Foundation of China (No. 81974017) and Tongji Hospital Self-Raised Fund (No. 2020JZKT157).

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  1. Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Key Laboratory of Organ Transplantation, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Huazhong University of Science and Technology, Ministry of Education, Chinese Academy of Medical Sciences, 1095 Jiefang Road, Wuhan, Hubei, 430030, China

    Zhimiao Zou, Minghui Zhao, Yang Yang, Yalong Xie, Zeyang Li, Liang Zhou, Runshi Shang & Ping Zhou

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ZMZ and MHZ wrote the manuscript. YY, YLX, ZYL, LZ, and RSS revised and corrected the manuscript. ZMZ and PZ conceived the original idea and supervised the project. PZ helped shape the manuscript. The authors read and approved the final manuscript.

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Zou, Z., Zhao, M., Yang, Y. et al. The role of pyroptosis in hepatocellular carcinoma. Cell Oncol. 46, 811–823 (2023). https://doi.org/10.1007/s13402-023-00787-9

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