The significance of PAK4 in signaling and clinicopathology: A review

Abstract

P21-activated protein kinases (PAKs) are thought to be at the center of tumor signaling pathways. As a representative member of the group II PAK family, P21-activated protein kinase 4 (PAK4) plays an important role in the development of tumors, with several biological functions such as participating in oncogenic transformation, promoting cell division, resisting aging and apoptosis, regulating cytoskeleton and adhesion, as well as suppressing antitumor immune responses. PAK4 is also crucial in biological processes, including the occurrence, proliferation, survival, migration, invasion, drug resistance, and immune escape of tumor cells. It is closely related to poor prognosis and tumor-related pathological indicators, which have significant clinical and pathological significance. Therefore, this article offers a review of the structure, activation, and biological functions of PAK4 and its clinical and pathological importance. This overview should be of assistance for future research on PAK4 and tumors and provide new ideas for tumor treatment and prognostic evaluation of patients.

Expression Patterns of PAK4 and PHF8 Are Associated with the Survival of Gallbladder Carcinoma Patients

“…The prognostic impact of the expression of PAK4 and PHF8 might be associated with their role in cancer progression. Both PAK4 and PHF8 have roles in the regulation of various cellular processes that are involved in cancer progression, including cell proliferation, survival from apoptosis, migration, angiogenesis, metabolic regulation, and immune evasion of cancer cells [ 2 , 4 , 5 , 15 , 16 , 17 , 18 , 34 ]. A higher expression of PAK4 promoted proliferation and invasiveness through activation of the PI3K/AKT pathway in breast cancer cells [ 6 ] and through c-Src and the EGFR pathway in ovarian cancer cells [ 8 ].…”

“…P21-activated kinase 4 (PAK4) is a serine/threonine kinase that participates in regulating cell signaling pathways, including tumorigenesis [ 1 , 2 ]. The expression of PAK4 has been shown to be involved in cancer progression [ 2 , 3 , 4 ]. PAK4 expression was higher in cancer tissue and a higher expression was related to a more aggressive phenotype and a poorer prognosis in various human cancers [ 5 , 6 , 7 , 8 , 9 ].…”

“…PAK4 expression was higher in cancer tissue and a higher expression was related to a more aggressive phenotype and a poorer prognosis in various human cancers [ 5 , 6 , 7 , 8 , 9 ]. The mechanism of PAK4 in cancer progression has been suggested by its role in regulating various aspects of cancer cell behavior, such as proliferation, invasiveness, angiogenesis, metabolic reprogramming, and immune evasion [ 3 , 4 ]. In addition, inhibition of PAK4 was presented as a therapeutic strategy for human cancers [ 3 , 10 ] and PAK4 inhibitors showed antitumor activity in the breast [ 11 ], pancreas [ 12 ], and colorectal cancers [ 13 ].…”

Cracking the Code of Neuronal Cell Fate

“…Among these were genes known for their contribution in the regulation of neuronal development and survival (i.e., Pak4 , Ntrk1 , Twist2 , Masp2 , Hoxd9 , Sstr2 , Sstr3 , Tep1 , Tyrp1 ) ( Figure 1 ) [ 44 , 45 , 45 , 46 , 47 , 48 ]. The p21 activated kinase Pak4 plays a pivotal role in neuronal pathophysiology, promoting the activity of transcription factors involved in cell survival, such as Akt and Cepbp and, thus, contributing to a wide range of intracellular processes including cytoskeletal dynamics, neuronal development, axonal outgrowth and neuronal survival [ 49 , 50 , 51 ]. Down-regulated expression of Pak4 has been associated with neurodegenerative disorders, including Amyotrophic Lateral Sclerosis and Parkinson’s disease, and it has been proposed as a therapeutic target against cancer and neurodegeneration [ 52 , 53 , 54 , 55 ].…”

Novel anthraquinone amino derivatives as anticancer agents targeting the human serine/threonine kinase PAK4

“…It has also been shown to be overexpressed in tumors, including breast, prostate, gastric, lung, ovarian, and pancreatic cancers [13,14]. PAK4 plays important roles in the deregulation of proliferation, apoptosis, migration, adhesion and invasion in cancer cells, thereby promoting the overall development and spread of cancer [8,15,16]. It has been proposed that PAK4 may function as a hub molecule, thereby joining major cell signaling pathways, which may eventually lead to cancer progression through invasion, metastasis, survival, proliferation and drug resistance [8,17].…”