Regulation of Cancer Metastasis by PAK2

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2025 Jan 8

PMID 39769207

Authors

Megan Wu

Chandan Sarkar

Bin Guo

Affiliations

Soon will be listed here.

Abstract

PAK2 is a serine-threonine kinase and a member of the p21-activated kinase (PAK) family. PAK2 is activated by GTP-bound rho family GTPases, Rac, and Cdc42, and it regulates actin dynamics, cell adhesion to the extracellular matrix, and cell motility. In various types of cancers, PAK2 has been implicated in the regulation of cancer cell proliferation, cell cycle, and apoptosis. In addition, recent studies have shown that PAK2 plays an important role in cancer cell metastasis, indicating PAK2 as a potential therapeutic target. This review discusses recent discoveries on the functions of PAK2 in the regulation of various types of cancers. A better understanding of the mechanisms of function of PAK2 will facilitate future development of cancer therapies.

References

Song J, Wang T, Chi X, Wei X, Xu S, Yu M . Kindlin-2 Inhibits the Hippo Signaling Pathway by Promoting Degradation of MOB1. Cell Rep. 2019; 29(11):3664-3677.e5. DOI: 10.1016/j.celrep.2019.11.035. View

Singh A, Sharma N . Quantitative SWATH-Based Proteomic Profiling for Identification of Mechanism-Driven Diagnostic Biomarkers Conferring in the Progression of Metastatic Prostate Cancer. Front Oncol. 2020; 10:493. PMC: 7156536. DOI: 10.3389/fonc.2020.00493. View

Cheng T, Yang Y, Wang H, Tien Y, Shun C, Huang H . Pyruvate kinase M2 promotes pancreatic ductal adenocarcinoma invasion and metastasis through phosphorylation and stabilization of PAK2 protein. Oncogene. 2018; 37(13):1730-1742. DOI: 10.1038/s41388-017-0086-y. View

Zhou L, Ercolano E, Ammoun S, Schmid M, Barczyk M, Hanemann C . Merlin-deficient human tumors show loss of contact inhibition and activation of Wnt/β-catenin signaling linked to the PDGFR/Src and Rac/PAK pathways. Neoplasia. 2012; 13(12):1101-12. PMC: 3257450. DOI: 10.1593/neo.111060. View

Yang H, Li Z, Zhu S, Wang W, Zhang J, Zhao D . Molecular mechanisms of pancreatic cancer liver metastasis: the role of PAK2. Front Immunol. 2024; 15:1347683. PMC: 10853442. DOI: 10.3389/fimmu.2024.1347683. View

Licciulli S, Maksimoska J, Zhou C, Troutman S, Kota S, Liu Q . FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. J Biol Chem. 2013; 288(40):29105-14. PMC: 3790009. DOI: 10.1074/jbc.M113.510933. View

Tian L, Han F, Yang J, Ming X, Chen L . Long non‑coding RNA LINC01006 exhibits oncogenic properties in cervical cancer by functioning as a molecular sponge for microRNA‑28‑5p and increasing PAK2 expression. Int J Mol Med. 2021; 47(4). PMC: 7891833. DOI: 10.3892/ijmm.2021.4879. View

Zeng J, Wang S, Gao M, Lu D, Song S, Chen D . PAK2 is essential for chromosome alignment in metaphase I oocytes. Cell Death Dis. 2023; 14(2):150. PMC: 9947007. DOI: 10.1038/s41419-023-05585-7. View

Alberts S, Cervantes A, van de Velde C . Gastric cancer: epidemiology, pathology and treatment. Ann Oncol. 2003; 14 Suppl 2:ii31-6. DOI: 10.1093/annonc/mdg726. View

10.

Kumar R, Sanawar R, Li X, Li F . Structure, biochemistry, and biology of PAK kinases. Gene. 2016; 605:20-31. PMC: 5250584. DOI: 10.1016/j.gene.2016.12.014. View

11.

Iwakawa H, Tomari Y . The Functions of MicroRNAs: mRNA Decay and Translational Repression. Trends Cell Biol. 2015; 25(11):651-665. DOI: 10.1016/j.tcb.2015.07.011. View

12.

Jakobi R, Moertl E, Koeppel M . p21-activated protein kinase gamma-PAK suppresses programmed cell death of BALB3T3 fibroblasts. J Biol Chem. 2001; 276(20):16624-34. DOI: 10.1074/jbc.M007753200. View

13.

Huang Z, Traugh J, Bishop J . Negative control of the Myc protein by the stress-responsive kinase Pak2. Mol Cell Biol. 2004; 24(4):1582-94. PMC: 344192. DOI: 10.1128/MCB.24.4.1582-1594.2004. View

14.

Jia B, Li J, Song Y, Luo C . ACSL4-Mediated Ferroptosis and Its Potential Role in Central Nervous System Diseases and Injuries. Int J Mol Sci. 2023; 24(12). PMC: 10298642. DOI: 10.3390/ijms241210021. View

15.

Macek P, Cliff M, Embrey K, Holdgate G, Nissink J, Panova S . Myc phosphorylation in its basic helix-loop-helix region destabilizes transient α-helical structures, disrupting Max and DNA binding. J Biol Chem. 2018; 293(24):9301-9310. PMC: 6005445. DOI: 10.1074/jbc.RA118.002709. View

16.

Li T, Zhang J, Zhu F, Wen W, Zykova T, Li X . P21-activated protein kinase (PAK2)-mediated c-Jun phosphorylation at 5 threonine sites promotes cell transformation. Carcinogenesis. 2010; 32(5):659-66. PMC: 3086698. DOI: 10.1093/carcin/bgq271. View

17.

Nuche-Berenguer B, Ramos-Alvarez I, Jensen R . The p21-activated kinase, PAK2, is important in the activation of numerous pancreatic acinar cell signaling cascades and in the onset of early pancreatitis events. Biochim Biophys Acta. 2016; 1862(6):1122-36. PMC: 4846574. DOI: 10.1016/j.bbadis.2016.02.008. View

18.

Misra U, Deedwania R, Pizzo S . Binding of activated alpha2-macroglobulin to its cell surface receptor GRP78 in 1-LN prostate cancer cells regulates PAK-2-dependent activation of LIMK. J Biol Chem. 2005; 280(28):26278-86. PMC: 1201553. DOI: 10.1074/jbc.M414467200. View

19.

Senturk A, Sahin A, Armutlu A, Kiremit M, Acar O, Erdem S . Quantitative Phosphoproteomics Analysis Uncovers PAK2- and CDK1-Mediated Malignant Signaling Pathways in Clear Cell Renal Cell Carcinoma. Mol Cell Proteomics. 2022; 21(11):100417. PMC: 9637947. DOI: 10.1016/j.mcpro.2022.100417. View

20.

Li Q, Wu X, Guo L, Shi J, Li J . MicroRNA-7-5p induces cell growth inhibition, cell cycle arrest and apoptosis by targeting PAK2 in non-small cell lung cancer. FEBS Open Bio. 2019; 9(11):1983-1993. PMC: 6823280. DOI: 10.1002/2211-5463.12738. View