Qiu Xun, Xu Hanzhi, Wang Kai, Gao Fengqiang, Xu Xiao, He Hong
Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
Zhejiang University School of Medicine, Hangzhou 310058, China.
Cancers (Basel). 2023 Jan 16;15(2):551. doi: 10.3390/cancers15020551.
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.
p21激活激酶(PAKs)是丝氨酸苏氨酸激酶,在许多生物学过程中发挥重要作用,包括细胞生长、存活、细胞骨架组织、迁移和形态。最近,由于PAKs在各种细胞类型的多种信号通路中的作用,它们在肝脏疾病过程中出现,包括肝癌、肝缺血再灌注损伤、肝炎和肝纤维化。PAKs的激活促进肝癌的生长和转移,并导致肝癌对放疗和化疗的耐药性,从而导致患者生存率低下。PAKs在肝炎的发展和进展以及肝脏的其他病理过程如纤维化和缺血再灌注损伤中也发挥重要作用。在这篇综述中,我们总结了目前关于PAKs在肝脏疾病中的作用及相关机制的研究,并进一步探讨了PAK抑制剂在肝脏疾病中的潜在治疗应用,旨在全面概述PAKs在肝脏疾病中的当前进展和前景。