ArticleOncogene2013
p21-Activated kinase 4 promotes prostate cancer progression through CREB.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 100 citations in OpenAlex.
- PAK4 in metabolic diseases: regulation by nutrient signals and therapeutic implications.Experimental & molecular medicine · 2026Review
- β2-Adrenergic receptor regulates osteoblast differentiation and migration and C-terminal β-catenin phosphorylation.Biochemical and biophysical research communications · 2025Article
- PAK4 phosphorylates cyclin-dependent kinase 2 to promote the GExperimental & molecular medicine · 2025Article
- Review
- p21-activated kinase 4 counteracts PKA-dependent lipolysis by phosphorylating FABP4 and HSL.Nature metabolism · 2024Article
- 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
- ß-Adrenoreceptors in Human Cancers.International journal of molecular sciences · 2023Review
- P21-Activated Kinase 4 Pak4 Maintains Embryonic Stem Cell Pluripotency via Akt Activation.Stem cells (Dayton, Ohio) · 2022Article
- Review
- Activation of the CREB Coactivator CRTC2 by Aberrant Mitogen Signaling promotes oncogenic functions in HPV16 positive head and neck cancer.Neoplasia (New York, N.Y.) · 2022Article
- Review
- Norepinephrine promotes glioma cell migration through up-regulating the expression of Twist1.BMC cancer · 2022Article
- CDK15 promotes colorectal cancer progression via phosphorylating PAK4 and regulating β-catenin/ MEK-ERK signaling pathway.Cell death and differentiation · 2022Article
- p21-activated kinase 4 phosphorylates peroxisome proliferator-activated receptor Υ and suppresses skeletal muscle regeneration.Journal of cachexia, sarcopenia and muscle · 2021Article
- hsa-miR-199a-3p Inhibits Motility, Invasiveness, and Contractility of Ovarian Endometriotic Stromal Cells.Reproductive sciences (Thousand Oaks, Calif.) · 2021Article
- Chronic stress promotes glioma cell proliferation via the PI3K/Akt signaling pathway.Oncology reports · 2021Article
- cAMP Response Element Binding-Protein- and Phosphorylation-Dependent Regulation of Tyrosine Hydroxylase by PAK4: Implications for Dopamine Replacement Therapy.Molecules and cells · 2021Article
- Expression of phosphorylated p21-activated kinase 4 is associated with aggressive histologic characteristics and poor prognosis in patients with surgically treated renal cell carcinoma.Investigative and clinical urology · 2021Article
- PAK4 suppresses motor neuron degeneration in hSOD1Cell proliferation · 2021Article
- p21-activated kinases as viable therapeutic targets for the treatment of high-risk Ewing sarcoma.Oncogene · 2021Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Prostate cancer is initially androgen-dependent but, over time, usually develops hormone- and chemo-resistance. The present study investigated a role for p21-activated kinase 4 (PAK4) in prostate cancer progression. PAK4 activation was markedly inhibited by H89, a specific protein kinase A (PKA) inhibitor, and PAK4 was activated by the elevation of cAMP. The catalytic subunit of PKA interacted with the regulatory domain of PAK4, and directly phosphorylated PAK4 at serine 474 (S474). Catalytically active PAK4 enhanced the transcriptional activity of CREB independent of S133 phosphorylation. Stable knockdown of PAK4 in PC-3 and DU145 prostate cancer cells inhibited tumor formation in nude mice. Decreased tumorigenicity correlated with decreased expression of CREB and its targets, including Bcl-2 and cyclin A1. Additionally, in androgen-dependent LNCap-FGC cells, PAK4 regulated cAMP-induced neuroendocrine differentiation, which is known to promote tumor progression. Finally, PAK4 enhanced survival and decreased apoptosis following chemotherapy. These results suggested that PAK4 regulates progression toward hormone- and chemo-resistance in prostate cancer, and this study identified both a novel activation mechanism and potential downstream effector pathways. Therefore, PAK4 may be a promising therapeutic target in prostate cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.