ArticleOncogene2015
Transcriptional regulation of fibronectin by p21-activated kinase-1 modulates pancreatic tumorigenesis.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- The proteome of postsurgical pancreatic juice.Pancreas · 2015Trial
- Modulating PAK1: Accessory Proteins as Promising Therapeutic Targets.Biomolecules · 2025Review
- Review
- [Computer-aided prediction and molecular mechanism investigation of active components in compound Kushen injection inhibiting p21-activated kinase 1].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2024Article
- Review
- PAK1 overexpression promotes myxofibrosarcoma angiogenesis through STAT5B-mediatedInternational journal of biological sciences · 2023Article
- Review
- MCRS1 Expression Regulates Tumor Activity and Affects Survival Probability of Patients with Gastric Cancer.Diagnostics (Basel, Switzerland) · 2022Article
- Natural Compound Shikonin Is a Novel PAK1 Inhibitor and Enhances Efficacy of Chemotherapy against Pancreatic Cancer Cells.Molecules (Basel, Switzerland) · 2022Article
- Fibronectin-Mediated Inflammatory Signaling Through Integrin α5 in Vascular Remodeling.Journal of the American Heart Association · 2021Article
- Current progress, challenges and future prospects of indazoles as protein kinase inhibitors for the treatment of cancer.RSC advances · 2021Review
- ELK1 Enhances Pancreatic Cancer Progression Via LGMN and Correlates with Poor Prognosis.Frontiers in molecular biosciences · 2021Article
- In Vitro Modeling of the Tumor Microenvironment in Tumor Organoids.Tissue engineering and regenerative medicine · 2020Review
- Identification of a novel PAK1 inhibitor to treat pancreatic cancer.Acta pharmaceutica Sinica. B · 2020Article
- From Genetic Alterations to Tumor Microenvironment: The Ariadne's String in Pancreatic Cancer.Cells · 2020Review
- Fibronectin in Cancer: Friend or Foe.Cells · 2019Review
- PAK1 Expression in Pancreatic Cancer: Clinicopathological Characteristics and Prognostic Significance.Clinical Medicine Insights. Oncology · 2019Article
- p21-activated kinase signalling in pancreatic cancer: New insights into tumour biology and immune modulation.World journal of gastroenterology · 2018Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the eighth largest cause of cancer-related mortality across the world, with a median 5-year survival rate of less than 3.5%. This is partly because the molecules and the molecular mechanisms that contribute to PDAC are not well understood. Our goal is to understand the role of p21-activated kinase 1 (Pak1) signaling axis in the progression of PDAC. Pak1, a serine/threonine kinase, is a well-known regulator of cytoskeletal remodeling, cell motility, cell proliferation and cell survival. Recent reports suggest that Pak1 by itself can have an oncogenic role in a wide variety of cancers. In this study, we analyzed the expression of Pak1 in human pancreatic cancer tissues and found that Pak1 levels are significantly upregulated in PDAC samples as compared with adjacent normals. Further, to study the functional role of Pak1 in pancreatic cancer model systems, we developed stable overexpression and lentiviral short hairpin RNA-mediated knockdown (KD) clones of Pak1 and studied the changes in transforming properties of the cells. We also observed that Pak1 KD clones failed to form tumors in nude mice. By adopting a quantitative PCR array-based approach, we identified fibronectin, a component of the extracellular matrix and a mesenchymal marker, as a transcriptional target of Pak1 signaling. The underlying molecular mechanism of Pak1-mediated transformation includes its nuclear import and recruitment to the fibronectin promoter via interaction with nuclear factor-κB (NF-κB)-p65 complex. To our knowledge, this is the first study illustrating Pak1-NF-κB-p65-mediated fibronectin regulation as a potent tumor-promoting mechanism in KRAS intact model.
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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.