P-21 Activated Kinases in Liver Disorders

SIMPLE SUMMARY: Liver disorders, particularly liver cancer and hepatitis, are considered major public health challenges. Nearly 90% of patients with liver cancer are diagnosed at late stages of the disease, which reduces the treatment options, having a significant negative impact on patient survival. Hepatitis is one of major risk factors of liver cancer. The p21 Activated Kinases (PAKs) play important roles in various diseases, and thus become targets for therapeutical purpose. Their roles in liver disorders are emerging. This review highlights the importance of alteration of PAKs within liver disorders, emphasizes their effects on liver cancer and hepatitis, and discusses the potential therapeutical effect of PAKs in liver disorders. We aim to provide an overview on current progress of PAKs in liver diseases, and a useful guide to research into PAK inhibitors and the potential application. 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.