ArticleBiochimica et biophysica acta2015
P21 activated kinase-1 mediates transforming growth factor β1-induced prostate cancer cell epithelial to mesenchymal transition.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 51 citations in OpenAlex.
- MicroRNA-506 inhibits tumor growth and metastasis in nasopharyngeal carcinoma through the inactivation of the Wnt/β-catenin signaling pathway by down-regulating LHX2.Journal of experimental & clinical cancer research : CR · 2019Trial
- PAK1 inhibition synergistically enhances the anti-tumor efficacy of PARP inhibitors in ovarian cancers.Genes & diseases · 2026Article
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- Genome analysis uncovers an inverse correlation between alterations in P21-activated kinases and patient survival across multiple cancer types.Physiological reports · 2025Article
- The Role of Small Interfering RNAs in Hepatocellular Carcinoma.Journal of gastrointestinal cancer · 2024Review
- Tumor Necrosis Factor Receptor-Associated Factor 6 and Human Cancer: A Systematic Review of Mechanistic Insights, Functional Roles, and Therapeutic Potential.Journal of Cancer · 2024Review
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- MicroRNAs as the critical regulators of cell migration and invasion in thyroid cancer.Biomarker research · 2022Review
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- The role of cell division control protein 42 in tumor and non-tumor diseases: A systematic review.Journal of Cancer · 2022Review
- Review
- P21‑activated kinase 1 mediates angiotensin II‑induced differentiation of human atrial fibroblasts via the JNK/c‑Jun pathway.Molecular medicine reports · 2021Article
- Article
- Liposomes Targeting P21 Activated Kinase-1 (PAK-1) and Selective for Secretory Phospholipase AInternational journal of molecular sciences · 2020Article
- The Small GTPase RAC1B: A Potent Negative Regulator of-and Useful Tool to Study-TGFβ Signaling.Cancers · 2020Review
- Sterically stabilized liposomes targeting P21 (RAC1) activated kinase-1 and secreted phospholipase AOncology letters · 2020Article
- PAK1 inhibitor IPA-3 mitigates metastatic prostate cancer-induced bone remodeling.Biochemical pharmacology · 2020Article
- DEP Domain-Containing Protein 1B (DEPDC1B) Promotes Migration and Invasion in Pancreatic Cancer Through the Rac1/PAK1-LIMK1-Cofilin1 Signaling Pathway.OncoTargets and therapy · 2020Article
- P21-Activated Kinase 1: Emerging biological functions and potential therapeutic targets in Cancer.Theranostics · 2020Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Transforming growth factor beta (TGFβ) is believed to play a dual role in prostate cancer. Molecular mechanism by which TGFβ1 suppresses early prostate tumor growth and induces epithelial-to-mesenchymal transition (EMT) in advanced stages is not known. We determined if P21-activated kinase1 (Pak1), which mediates cytoskeletal remodeling is necessary for the TGFβ1 induced prostate cancer EMT. Effects of TGFβ1 on control prostate cancer PC3 and DU145 cells and those with IPA 3 and siRNA mediated Pak1 inhibition were tested for prostate tumor xenograft in vivo and EMT in vitro. TGFβ1 inhibited PC3 tumor xenograft growth via activation of P38-MAPK and caspase-3, 9. Long-term stimulation with TGFβ1 induced PC3 and DU145 cell scattering and increased expression of EMT markers such as Snail and N-cadherin through tumor necrosis factor receptor-associated factor-6 (TRAF6)-mediated activation of Rac1/Pak1 pathway. Selective inhibition of Pak1 using IPA 3 or knockdown using siRNA both significantly inhibited TGFβ1-induced prostate cancer cell EMT and expression of mesenchymal markers. Our study demonstrated that TGFβ1 induces apoptosis and EMT in prostate cancer cells via activation of P38-MAPK and Rac1/Pak1 respectively. Our results reveal the potential therapeutic benefits of targeting TGFβ1-Pak1 pathway for advanced-stage 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.