P-21 Activated Kinases in Liver Disorders
Abstract
:Simple Summary
Abstract
1. Introduction
2. Structure and Activation of PAKs Family
3. PAKs in Liver Cancers
3.1. Roles of Group I PAKs in Liver Cancer
3.2. Roles of Group II PAKs in Liver Cancer
4. PAKs in Hepatic Ischemia/Reperfusion Injury
5. PAKs in Hepatitis
6. PAKs in Liver Fibrosis
7. Therapeutic Effects of PAK Inhibitors in Liver Disorders
8. Discussion
8.1. Potential Role of PAKs in Glucolipid Metabolism of Liver
8.2. Potential Role of PAKs in Immunotherapy for Liver Disorders
9. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Liver Disorders | Group I PAKs | Group II PAKs |
---|---|---|
Liver cancer | PAK1: β-catenin → Proliferation/invasion↑ and apoptosis↓ MAPK/ERK, PI3K/AKT → Apoptosis↓ Snail → Migration and invasion↑ Snail, β-catenin, p53/p21 → Xenograft tumor growth↑ Paxillin, JNK → Actin stress fibers and metastasis↑ Anchorage-independent growth and anoikis resistance ↑ HIF-1α, Vimentin → Vasculogenic mimicry↑ PAK2: Migration↑ PAK3: TGF-β/Smad → EMT↑ | PAK4: Caspase-8, NF-κB → Apoptosis↓ RAF/MEK/ERK → Tumor growth and metastasis↑ P53 → Migration and invasion↑ PAK5: Proliferation and invasion↑ Apoptosis induced by cisplatin↓ β-catenin/ABCB1 → Resistance to adriamycin, 5-fluorouracil and sorafenib↑ Radiotherapy resistance↑ PAK6: Proliferation↑ Eg5 → mitosis↑ HCC metastasis↑ |
Liver IRI | PAK1: VEGFα, IGF1 → IRI↓ | PAK4: Nrf2 → Inflammation and necrosis of hepatocytes↑ |
Hepatitis | PAK1: RAF-1 → HBV X protein → Apoptosis↓ HCV replication↓ NMIIA/Cofilin → HEV infection↑ NF-κB/IRF1/IL-6 → The differentiation of CD4+ T cells to Th17 cells and inflammation in Schistosoma japonicum infection↑ Autoimmune hepatitis progression↑ PAK2: Apoptosis and inflammatory reaction in cells infected with HCV↓ PAK3: HBV replication↑ | PAK6: Tumorigenesis in alcoholic hepatitis↑ |
Liver fibrosis | PAK1: Integrin β-1 → Myofibroblasts activation and ECM production↑ PAK2: Myofibroblast activation and liver fibrosis↑ PAK3: Integrin β-1 → Myofibroblasts activation and ECM production↑ | PAK4: Perisinusoidal/pericellular fibrosis↑ |
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Qiu, X.; Xu, H.; Wang, K.; Gao, F.; Xu, X.; He, H. P-21 Activated Kinases in Liver Disorders. Cancers 2023, 15, 551. https://doi.org/10.3390/cancers15020551
Qiu X, Xu H, Wang K, Gao F, Xu X, He H. P-21 Activated Kinases in Liver Disorders. Cancers. 2023; 15(2):551. https://doi.org/10.3390/cancers15020551
Chicago/Turabian StyleQiu, Xun, Hanzhi Xu, Kai Wang, Fengqiang Gao, Xiao Xu, and Hong He. 2023. "P-21 Activated Kinases in Liver Disorders" Cancers 15, no. 2: 551. https://doi.org/10.3390/cancers15020551