P-21 Activated Kinases in Liver Disorders

Cancers (Basel). 2023 Jan 16;15(2):551. doi: 10.3390/cancers15020551.

Abstract

The p21 Activated Kinases (PAKs) are serine threonine kinases and play important roles in many biological processes, including cell growth, survival, cytoskeletal organization, migration, and morphology. Recently, PAKs have emerged in the process of liver disorders, including liver cancer, hepatic ischemia-reperfusion injury, hepatitis, and liver fibrosis, owing to their effects in multiple signaling pathways in various cell types. Activation of PAKs promotes liver cancer growth and metastasis and contributes to the resistance of liver cancer to radiotherapy and chemotherapy, leading to poor survival of patients. PAKs also play important roles in the development and progression of hepatitis and other pathological processes of the liver such as fibrosis and ischemia-reperfusion injury. In this review, we have summarized the currently available studies about the role of PAKs in liver disorders and the mechanisms involved, and further explored the potential therapeutic application of PAK inhibitors in liver disorders, with the aim to provide a comprehensive overview on current progress and perspectives of PAKs in liver disorders.

Keywords: hepatic ischemia-reperfusion injury; hepatitis; liver cancer; liver fibrosis; p21 Activated Kinase; small molecular inhibitors.

Publication types

  • Review

Grants and funding

This study was funded by Zhejiang Provincial Natural Science Foundation, Grant LY22H160048; the Youth Program of the National Natural Science Foundation of China, Grant 82003248; the Key Research & Development Plan of Zhejiang Province, Grant 2019C03050; and the Major Research Plan of the National Natural Science Foundation of China, Grant 92159202.