ArticleJournal of experimental & clinical cancer research : CR2015
Overexpression of P21-activated kinase 4 is associated with poor prognosis in non-small cell lung cancer and promotes migration and invasion.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 67 citations in OpenAlex.
- The interplay between p21-activated kinases and tumour-infiltrating dendritic cells and T cells and its implication in pancreatic cancer immunotherapy.Cell communication and signaling : CCS · 2026Review
- P21-activated kinase 4: a potent oncogene, molecular mechanisms and opportunities for targeted therapy.Cancer cell international · 2025Review
- PAK4 phosphorylates cyclin-dependent kinase 2 to promote the GExperimental & molecular medicine · 2025Article
- Circular RNA circLIMK1-005 promotes the progression of lung adenocarcinoma by interacting with RPA1 protein to activate CDK4 signaling.Cell death discovery · 2025Article
- Red blood cell-tumor cell interactions promote tumor cell progression.Journal of experimental & clinical cancer research : CR · 2025Article
- Identification of Potential Selective PAK4 Inhibitors Through Shape and Protein Conformation Ensemble Screening and Electrostatic-Surface-Matching Optimization.Current issues in molecular biology · 2025Article
- Inhibition of NAMPT by PAK4 Inhibitors.International journal of molecular sciences · 2024Article
- Targeting PAK4 reverses cisplatin resistance in NSCLC by modulating ER stress.Cell death discovery · 2024Article
- Genetic alterations shape innate immune cells to foster immunosuppression and cancer immunotherapy resistance.Clinical and experimental medicine · 2023Review
- Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers.Molecular cancer therapeutics · 2023Article
- Review
- New Immunohistochemical Markers for Pleural Mesothelioma Subtyping.Diagnostics (Basel, Switzerland) · 2023Article
- P21-Activated Kinase 4 Pak4 Maintains Embryonic Stem Cell Pluripotency via Akt Activation.Stem cells (Dayton, Ohio) · 2022Article
- Review
- Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells.Acta pharmaceutica Sinica. B · 2022Article
- The significance of PAK4 in signaling and clinicopathology: A review.Open life sciences · 2022Review
- hsa-miR-199a-3p Inhibits Motility, Invasiveness, and Contractility of Ovarian Endometriotic Stromal Cells.Reproductive sciences (Thousand Oaks, Calif.) · 2021Article
- PAK4 methylation by the methyltransferase SETD6 attenuates cell adhesion.Scientific reports · 2020Article
- Recognition of physiological phosphorylation sites by p21-activated kinase 4.Journal of structural biology · 2020Article
- The Functional Effects of Key Driver KRAS Mutations on Gene Expression in Lung Cancer.Frontiers in genetics · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundP21-activated kinase 4 (PAK4), an effector of the Rho family protein Cdc42, is an important oncogene whose expression is increased in many human cancers and is generally positively correlated with advanced disease and decreased survival. However, little is known about the expression and biological function of PAK4 in human non-small cell lung cancer (NSCLC).
methodsPAK4 expression in NSCLC tissues and adjacent non-tumor tissues were assessed by immunohistochemistry, real-time PCR, and western blotting. Prognostic value of PAK4 expression was evaluated by Kaplan-Meier analysis and Cox regression. siRNA-mediated gene silencing and protein kinase assay was applied to demonstrate the role and the mechanism of PAK4 in lung cancer cell migration, invasion.
resultsThe results showed that PAK4 was overexpressed in NSCLC cell lines and human NSCLC tissues. PAK4 expression was detected both in the membranes and cytoplasm of NSCLC cancer cells in vivo. Moreover, increased expression of PAK4 was associated with metastasis, shorter overall survival, advanced stage of NSCLC. Furthermore, PAK4 expression was positively correlated with phosphorylation of LIMK1 expression levels. Knockdown of PAK4 in NSCLC cell lines led to reduce the phosphorylation of LIMK1, which resulted in decrease of the cell migration and invasion. In addition, PAK4 bound to LIMK1 directly and activated it via phosphorylation.
conclusionsThese data demonstrate that PAK4 mediated LIMK1 phosphorylation regulates the migration and invasion in NSCLC. Therefore, PAK4 might be a significant prognostic marker and potential therapeutic molecular target in NSCLC.
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