ArticleOncogene2014
Oncogenic PAK4 regulates Smad2/3 axis involving gastric tumorigenesis.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 57 citations in OpenAlex.
- The Role of the p21-Activated Kinase Family in Tumor Immunity.International journal of molecular sciences · 2025Review
- Article
- Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Editorial: The culprit behind some diseases: overexpression/hyperactivity of G6PD.Frontiers in pharmacology · 2024Article
- Review
- CORO1C, a novel PAK4 binding protein, recruits phospho-PAK4 at serine 99 to the leading edge and promotes the migration of gastric cancer cells.Acta biochimica et biophysica Sinica · 2022Article
- The significance of PAK4 in signaling and clinicopathology: A review.Open life sciences · 2022Review
- PRPF6 promotes androgen receptor/androgen receptor-variant 7 actions in castration-resistant prostate cancer cells.International journal of biological sciences · 2021Article
- p21-activated kinase 4 promotes the progression of esophageal squamous cell carcinoma by targeting LASP1.Molecular carcinogenesis · 2020Article
- Phosphorylation Sites in Protein Kinases and Phosphatases Regulated by Formyl Peptide Receptor 2 Signaling.International journal of molecular sciences · 2020Review
- SMADs binding site polymorphisms rs9911630 is associated with susceptibility but not prognosis of gastric cancer: a case control study.Journal of Cancer · 2020Article
- Fisetin Modulates Human Oral Squamous Cell Carcinoma Proliferation by Blocking PAK4 Signaling Pathways.Drug design, development and therapy · 2020Article
- Bioinformatic analysis of next‑generation sequencing data to identify dysregulated genes in fibroblasts of idiopathic pulmonary fibrosis.International journal of molecular medicine · 2019Article
- Overexpression of c-Ski promotes cell proliferation, invasion and migration of gastric cancer associated fibroblasts.The Kaohsiung journal of medical sciences · 2019Article
- PAK4, a target of miR-9-5p, promotes cell proliferation and inhibits apoptosis in colorectal cancer.Cellular & molecular biology letters · 2019Article
- Epigenetic Field Cancerization in Gastric Cancer: microRNAs as Promising Biomarkers.Journal of Cancer · 2019Article
- Article
- P21-activated kinase 4 in pancreatic acinar cells is activated by numerous gastrointestinal hormones/neurotransmitters and growth factors by novel signaling, and its activation stimulates secretory/growth cascades.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- MiR-199a/b-3p inhibits gastric cancer cell proliferation via down-regulating PAK4/MEK/ERK signaling pathway.BMC cancer · 2018Article
- PAK4 enhances TGF-β1-induced epithelial-mesenchymal transition through activating β-catenin signaling pathway in renal tubular epithelial cells.International journal of clinical and experimental pathology · 2018Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The alteration of p21-activated kinase 4 (PAK4) and transforming growth factor-beta (TGF-β) signaling effector Smad2/3 was detected in several types of tumors, which acts as oncogenic factor and tumor suppressor, but the relationship between these events has not been explored. Here, we demonstrate that PAK4 interacts with and modulates phosphorylation of Smad2/3 via both kinase-dependent and kinase-independent mechanisms, which attenuate Smad2/3 axis transactivation and TGF-β-mediated growth inhibition in gastric cancer cells. First, PAK4 interaction with Smad2/3, which is independent of PAK4 kinase activity, blocks TGF-β1-induced phosphorylation of Smad2 Ser465/467 or Smad3 Ser423/425 and the consequent activation. In addition, PAK4 phosphorylates Smad2 on Ser465, leading to the degradation of Smad2 through ubiquitin-proteasome-dependent pathway under hepatocyte growth factor (HGF) stimulation. Interestingly, PAK4 expression correlates negatively with phospho-Ser465/467 Smad2 but positively with phospho-Ser465 Smad2 in gastric cancer tissues. Furthermore, the expressions of HGF, phospho-Ser474 PAK4 and phospho-Ser465 Smad2 are markedly increased in gastric cancer tissues, and the expression of Smad2 is decreased in gastric cancer tissues. Our results document an oncogenic role of PAK4 in repression of Smad2/3 transactivation that involved in tumorigenesis, and suggest PAK4 as a potential therapeutic target for gastric cancer.
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