ArticleThe Prostate2010
Inhibition of p21-activated kinase 6 (PAK6) increases radiosensitivity of prostate cancer cells.
Article in The Prostate, 2010. 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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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
35 citing papers in PubMed, 49 citations in OpenAlex.
- Diversity of antigen-specific responses induced in vivo with CTLA-4 blockade in prostate cancer patients.Journal of immunology (Baltimore, Md. : 1950) · 2012Trial
- Ethanol extract of Vanilla planifolia stems reduces PAK6 expression and induces cell death in glioblastoma cells.Journal of cellular and molecular medicine · 2024Article
- The synergistic effects of betanin and radiotherapy in a prostate cancer cell line: an in vitro study.Molecular biology reports · 2023Article
- Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic Sensitivity.Biomedicines · 2023Review
- PAK6 promotes homologous-recombination to enhance chemoresistance to oxaliplatin through ATR/CHK1 signaling in gastric cancer.Cell death & disease · 2022Article
- Targeting of p21-Activated Kinase 4 Radiosensitizes Glioblastoma Cells via Impaired DNA Repair.Cells · 2022Article
- Integration of immune and hypoxia gene signatures improves the prediction of radiosensitivity in breast cancer.American journal of cancer research · 2022Article
- In silico comparative analysis of LRRK2 interactomes from brain, kidney and lung.Brain research · 2021Article
- Review
- Gene Expression Profile of the Human Colorectal Carcinoma LoVo Cells Treated With Sporamin and Thapsigargin.Frontiers in oncology · 2021Article
- Estrogen receptor alpha (ERα)-mediated coregulator binding and gene expression discriminates the toxic ERα agonist diethylstilbestrol (DES) from the endogenous ERα agonist 17β-estradiol (E2).Cell biology and toxicology · 2020Article
- Coordinated dysregulation of cancer progression by the HER family and p21-activated kinases.Cancer metastasis reviews · 2020Review
- PAK6 promotes cervical cancer progression through activation of the Wnt/β-catenin signaling pathway.Oncology letters · 2020Article
- Mitochondrial PAK6 inhibits prostate cancer cell apoptosisTheranostics · 2020Article
- Identification of differentially expressed genes in cervical cancer by bioinformatics analysis.Oncology letters · 2018Article
- Melanoma-associated mutants within the serine-rich domain of PAK5 direct kinase activity to mitogenic pathways.Oncotarget · 2018Article
- APIM-peptide targeting PCNA improves the efficacy of docetaxel treatment in the TRAMP mouse model of prostate cancer.Oncotarget · 2018Article
- Regulation of neuronal survival by DNA methyltransferases.Neural regeneration research · 2017Review
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- Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundp21-activated kinase 6 (PAK6) is a serine/threonine kinase belonging to the p21-activated kinase (PAK) family. We investigated the role of PAK6 in radiation-induced cell death in human prostate cancer cells.
methodsWe used a short hairpin RNA (shRNA) strategy to stably knock down PAK6 in PC3 and DU145 cells. Radiation sensitivities were compared in PAK6 stably knockdown cells versus the scrambled shRNA-expressing control cells.
resultsPAK6 mRNA and protein levels in PC3 and DU145 cells were upregulated upon exposure to 6 Gy of radiation. After irradiation, an increased percentage of apoptotic cells and cleaved caspase-3 levels were demonstrated in combination with a decrease in cell viability and a reduction in clonogenic survival in PAK6-knockdown cells. In addition, transfection with PAK6 shRNA blocked cells in a more radiosensitive G2-M phase and increased levels of DNA double-strand breaks. We further explored the potential mechanisms by which PAK6 mediates resistance to radiation-induced apoptosis. Inhibition of PAK6 caused a decrease in Ser(112) phosphorylation of BAD, a proapoptotic member of the Bcl-2 family, which led to enhanced binding of BAD to Bcl-2 and Bcl-X(L) and release of cytochrome c culminating into caspase activation and cell apoptosis.
conclusionsThe combination of PAK6 inhibition and irradiation resulted in significantly decreased survival of prostate cancer cells. The underlying mechanisms by which targeting PAK6 may improve radiation response seem to be multifaceted, and involve alterations in cell cycle distribution and impaired DNA double-strand break repair as well as relieved BAD phosphorylation.
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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.