ArticleCancer research2012
p21-Activated kinase 1 is required for efficient tumor formation and progression in a Ras-mediated skin cancer model.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
81 citing papers in PubMed, 160 citations in OpenAlex.
- Urine miRNAs: potential biomarkers for monitoring progression of early stages of diabetic nephropathy.Medical hypotheses · 2013Trial
- Inhibitors of De Novo Guanylate Biosynthesis Enhance the Potency of MAPK Cascade Inhibitors Against Colorectal Cancer.International journal of molecular sciences · 2025Article
- Inhibition of the RAC/PAK Signaling Axis Enhances the Potency of MAPK Cascade Inhibitors Against Uveal Melanoma.Biomolecules · 2025Article
- Integrated spatial and single-cell transcriptomics reveal PAK kinase as a therapeutic target in fibroblastic foci and dense fibrosis of idiopathic pulmonary fibrosis.The European respiratory journal · 2025Article
- KRAS Mutations in Cancer: Understanding Signaling Pathways to Immune Regulation and the Potential of Immunotherapy.Cancers · 2025Review
- Recent Anti-KRASCancers · 2025Review
- Review
- Discovery of a Novel Selective PAK1/HDAC6/HDAC10 Inhibitor ZMF-25 that Induces Mitochondrial Metabolic Breakdown and Autophagy-Related Cell Death in Triple-Negative Breast Cancer.Research (Washington, D.C.) · 2025Article
- PAK1 and Therapy Resistance in Melanoma.Cells · 2023Review
- Exploring Nanocarriers as Treatment Modalities for Skin Cancer.Molecules (Basel, Switzerland) · 2023Review
- Review
- Development and Utility of a PAK1-Selective Degrader.Journal of medicinal chemistry · 2022Article
- Comprehensive analysis of the prognostic implications and functional exploration of PAK gene family in human cancer.Cancer cell international · 2022Article
- [Blocking PAK1 kinase activity promotes the differentiation of acute megakaryocytic leukemia cells and induces their apoptosis].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2022Article
- Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient-Derived Xenografts and Direct-from-Patient Screening.Cancer discovery · 2021Article
- Proximity proteomics identifies PAK4 as a component of Afadin-Nectin junctions.Nature communications · 2021Article
- Current progress, challenges and future prospects of indazoles as protein kinase inhibitors for the treatment of cancer.RSC advances · 2021Review
- Targeting effector pathways in RAC1Small GTPases · 2021Article
- Aberrant Rac pathway signalling in glioblastoma.Small GTPases · 2021Review
- CDK4/6 inhibition synergizes with inhibition of P21-Activated Kinases (PAKs) in lung cancer cell lines.PloS one · 2021Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
The RAS genes are the most commonly mutated oncogenes in human cancer and present a particular therapeutic dilemma, as direct targeting of Ras proteins by small molecules has proved difficult. Signaling pathways downstream of Ras, in particular Raf/Mek/Erk and PI3K/Akt/mTOR, are dominated by lipid and protein kinases that provide attractive alternate targets in Ras-driven tumors. As p21-activated kinase 1 (Pak1) has been shown to regulate both these signaling pathways and is itself upregulated in many human cancers, we assessed the role of Pak1 in Ras-driven skin cancer. In human squamous cell carcinoma (SCC), we found a strong positive correlation between advanced stage and grade and PAK1 expression. Using a mouse model of Kras-driven SCC, we showed that deletion of the mouse Pak1 gene led to markedly decreased tumorigenesis and progression, accompanied by near total loss of Erk and Akt activity. Treatment of Kras(G12D) mice with either of two distinct small molecule Pak inhibitors (PF3758309 and FRAX597) caused tumor regression and loss of Erk and Akt activity. Tumor regression was also seen in mice treated with a specific Mek inhibitor, but not with an Akt inhibitor. These findings establish Pak1 as a new target in KRAS-driven tumors and suggest a mechanism of action through the Erk, but not the Akt, signaling pathway.
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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.