Endoplasmic Reticulum Stress Signaling and the Pathogenesis of Hepatocarcinoma
Abstract
:1. Introduction
2. ER Stress and UPR
2.1. Serine/Threonine-Protein Kinase/Endoribonuclease IRE1α and Transcription Factor Xbp1s
2.2. The Kinase PERK and Transcription Factor ATF4 and CHOP
2.3. Transcription Factor ATF6α
2.4. Transcription Factor CREBH
3. Pathogenesis of Hepatocellular Carcinoma
3.1. Viral Hepatitis
3.2. Alcoholic Fatty Liver Disease (ALD)
3.3. Non-Alcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH)
3.4. Alpha1-Antitrypsin Deficiency (AATD)
4. Targeting ER Stress for HCC Treatment
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Risk Factor | UPR Pathway Activation | Cellular and Molecular Mechanisms of Liver Injury | Reference |
---|---|---|---|
Hepatitis B virus | PERK-ATF4 | Oxidative stress and apoptosis | [97] |
ATF6 cleavage | Proliferation of hepatocellular carcinoma cells | [98,99] | |
IRE1α-XBP1s | |||
Hepatitis C virus | IRE1α-XBP1s | Misfolded proteins are more stable | [103] |
IRE1α-JNK | TGFβ1 expression and proliferation | [101,105] | |
CREBH cleavage | |||
PERK pathway | Autophagy induction | [104] | |
ATF6 cleavage | |||
Alcohol | PERK-ATF4-CHOP | Apoptosis | [106] |
NNMT expression | [107] | ||
ATF6 cleavage | Lipogenesis and steatosis | [108] | |
CREBH cleavage | Perturbation of bile acid homeostasis | [109] | |
fatty liver (NAFLD/NASH) | IRE1α-XBP1s | Hepatic steatosis and insulin resistance | [110] |
miRNA expression and liver injury | |||
PERK-ATF4 | SCD1 and CYP2E1 expression; liver steatosis | [111,112] | |
ATF6 cleavage | Hepatic steatosis and insulin resistance | [74] | |
CREBH cleavage | Nonalcoholic steatohepatitis | [80] | |
IREα—JNKs and NF-κB | Hepatic injury and fibrosis | [113] | |
Alpha1-antitrypsin deficiency (AATD) | CHOP | Upregulates A1AT expression and apoptosis | [114] |
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Wei, J.; Fang, D. Endoplasmic Reticulum Stress Signaling and the Pathogenesis of Hepatocarcinoma. Int. J. Mol. Sci. 2021, 22, 1799. https://doi.org/10.3390/ijms22041799
Wei J, Fang D. Endoplasmic Reticulum Stress Signaling and the Pathogenesis of Hepatocarcinoma. International Journal of Molecular Sciences. 2021; 22(4):1799. https://doi.org/10.3390/ijms22041799
Chicago/Turabian StyleWei, Juncheng, and Deyu Fang. 2021. "Endoplasmic Reticulum Stress Signaling and the Pathogenesis of Hepatocarcinoma" International Journal of Molecular Sciences 22, no. 4: 1799. https://doi.org/10.3390/ijms22041799