» Articles » PMID: 36230657

P21-Activated Kinase: Role in Gastrointestinal Cancer and Beyond

Overview
Journal Cancers (Basel)
Publisher MDPI
Specialty Oncology
Date 2022 Oct 14
PMID 36230657
Authors
Affiliations
Soon will be listed here.
Abstract

Gastrointestinal tumors are the most common tumors, and they are leading cause of cancer deaths worldwide, but their mechanisms are still unclear, which need to be clarified to discover therapeutic targets. p21-activating kinase (PAK), a serine/threonine kinase that is downstream of Rho GTPase, plays an important role in cellular signaling networks. According to the structural characteristics and activation mechanisms of them, PAKs are divided into two groups, both of which are involved in the biological processes that are critical to cells, including proliferation, migration, survival, transformation and metabolism. The biological functions of PAKs depend on a large number of interacting proteins and the signaling pathways they participate in. The role of PAKs in tumors is manifested in their abnormality and the consequential changes in the signaling pathways. Once they are overexpressed or overactivated, PAKs lead to tumorigenesis or a malignant phenotype, especially in tumor invasion and metastasis. Recently, the involvement of PAKs in cellular plasticity, stemness and the tumor microenvironment have attracted attention. Here, we summarize the biological characteristics and key signaling pathways of PAKs, and further analyze their mechanisms in gastrointestinal tumors and others, which will reveal new therapeutic targets and a theoretical basis for the clinical treatment of gastrointestinal cancer.

Citing Articles

The up-regulation of PAK2 indicates unfavorable prognosis in patients with serous epithelial ovarian cancer and contributes to paclitaxel resistance in ovarian cancer cells.

Shuang T, Wu S, Zhao Y, Yang Y, Pei M BMC Cancer. 2024; 24(1):1213.

PMID: 39350056 PMC: 11440729. DOI: 10.1186/s12885-024-12969-1.


FRAX486, a PAK inhibitor, overcomes ABCB1-mediated multidrug resistance in breast cancer cells.

Zhang M, Zeng X, She M, Dong X, Chen J, Xiong Q Braz J Med Biol Res. 2024; 57:e13357.

PMID: 38958364 PMC: 11221864. DOI: 10.1590/1414-431X2024e13357.


Targeting P21-Activated Kinase-1 for Metastatic Prostate Cancer.

Somanath P, Chernoff J, Cummings B, Prasad S, Homan H Cancers (Basel). 2023; 15(8).

PMID: 37190165 PMC: 10137274. DOI: 10.3390/cancers15082236.


Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic Sensitivity.

Sankaran D, Amjesh R, Paul A, George B, Kala R, Saini S Biomedicines. 2023; 11(2).

PMID: 36830998 PMC: 9953343. DOI: 10.3390/biomedicines11020462.

References
1.
Sells M, Chernoff J . Emerging from the Pak: the p21-activated protein kinase family. Trends Cell Biol. 1997; 7(4):162-7. DOI: 10.1016/S0962-8924(97)01003-9. View

2.
Ghosh A, Awasthi S, Peterson J, Hamburger A . Regulation of tamoxifen sensitivity by a PAK1-EBP1 signalling pathway in breast cancer. Br J Cancer. 2013; 108(3):557-63. PMC: 3593557. DOI: 10.1038/bjc.2013.11. View

3.
Chung J, Kim T, Kang Y, Yoon S, Kim Y, Lee S . PAK1 as a Potential Therapeutic Target in Male Smokers with EGFR-Mutant Non-Small Cell Lung Cancer. Molecules. 2020; 25(23). PMC: 7729550. DOI: 10.3390/molecules25235588. View

4.
Oladimeji P, Skerl R, Rusch C, Diakonova M . Synergistic Activation of ERα by Estrogen and Prolactin in Breast Cancer Cells Requires Tyrosyl Phosphorylation of PAK1. Cancer Res. 2016; 76(9):2600-11. PMC: 4873454. DOI: 10.1158/0008-5472.CAN-15-1758. View

5.
Zhang J, Zhang H, Wang J, You L, Zhou R, Zhao D . GL-1196 Suppresses the Proliferation and Invasion of Gastric Cancer Cells via Targeting PAK4 and Inhibiting PAK4-Mediated Signaling Pathways. Int J Mol Sci. 2016; 17(4):470. PMC: 4848926. DOI: 10.3390/ijms17040470. View