ArticlePloS one2012
Hypoxia-induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
What it found
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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.
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
87 citing papers in PubMed, 174 citations in OpenAlex.
- Trial
- Review
- HypoxamiRs in pancreatic cancer: master regulators of the hypoxic tumor microenvironment.Cell biology and toxicology · 2025Review
- Endothelial activation during the diapedesis of cancer cells: between the kiss of death and therapeutic breakthrough.Cellular & molecular biology letters · 2025Review
- Decoding the pancreatic cancer microenvironment: The multifaceted regulation of microRNAs.Clinical and translational medicine · 2025Review
- P4HA1 Mediates Hypoxia-Induced Invasion in Human Pancreatic Cancer Organoids.Cancer research communications · 2025Article
- Critical roles of miR-21 in promotions angiogenesis: friend or foe?Clinical and experimental medicine · 2025Review
- Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.Frontiers of medicine · 2025Review
- Molecular roles of microRNA-21 and exosomal miR-21 in gastrointestinal cancers: diagnostic, therapeutic, and drug resistance insights.Frontiers in molecular biosciences · 2025Review
- Three-Dimensional Tumor Models to Study Cancer Stemness-Mediated Drug Resistance.Cellular and molecular bioengineering · 2024Review
- Review
- Cancer Stem Cells in Carcinogenesis and Potential Role in Pancreatic Cancer.Current stem cell research & therapy · 2024Review
- Resveratrol: Targeting Cancer Stem Cells and ncRNAs to Overcome Cancer Drug Resistance.Current molecular medicine · 2024Review
- Regulation of Cancer-Associated miRNAs Expression under Hypoxic Conditions.Analytical cellular pathology (Amsterdam) · 2024Review
- LSD1 inhibition by tranylcypromine hydrochloride reduces alkali burn-induced corneal neovascularization and ferroptosis by suppressing HIF-1α pathway.Frontiers in pharmacology · 2024Article
- Cancer Stem Cells in Renal Cell Carcinoma: Origins and Biomarkers.International journal of molecular sciences · 2023Review
- Role of the long non-coding RNAs in regulation of Gemcitabine response in tumor cells.Cancer cell international · 2023Review
- Anticancer Activity of Novel Difluorinated Curcumin Analog and Its Inclusion Complex with 2-Hydroxypropyl-β-Cyclodextrin against Pancreatic Cancer.International journal of molecular sciences · 2023Article
- microRNAs Associated with Gemcitabine Resistance via EMT, TME, and Drug Metabolism in Pancreatic Cancer.Cancers · 2023Review
- Expression of Selected miRNAs in Normal and Cancer-Associated Fibroblasts and in BxPc3 and MIA PaCa-2 Cell Lines of Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2023Article
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Hypoxia is known to play critical roles in cell survival, angiogenesis, tumor invasion, and metastasis. Hypoxia mediated over-expression of hypoxia-inducible factor (HIF) has been shown to be associated with therapeutic resistance, and contributes to poor prognosis of cancer patients. Emerging evidence suggest that hypoxia and HIF pathways contributes to the acquisition of epithelial-to-mesenchymal transition (EMT), maintenance of cancer stem cell (CSC) functions, and also maintains the vicious cycle of inflammation-all which lead to therapeutic resistance. However, the precise molecular mechanism(s) by which hypoxia/HIF drives these events are not fully understood. Here, we show, for the first time, that hypoxia leads to increased expression of VEGF, IL-6, and CSC signature genes Nanog, Oct4 and EZH2 consistent with increased cell migration/invasion and angiogenesis, and the formation of pancreatospheres, concomitant with increased expression of miR-21 and miR-210 in human pancreatic cancer (PC) cells. The treatment of PC cells with CDF, a novel synthetic compound inhibited the production of VEGF and IL-6, and down-regulated the expression of Nanog, Oct4, EZH2 mRNAs, as well as miR-21 and miR-210 under hypoxia. CDF also led to decreased cell migration/invasion, angiogenesis, and formation of pancreatospheres under hypoxia. Moreover, CDF decreased gene expression of miR-21, miR-210, IL-6, HIF-1α, VEGF, and CSC signatures in vivo in a mouse orthotopic model of human PC. Collectively, these results suggest that the anti-tumor activity of CDF is in part mediated through deregulation of tumor hypoxic pathways, and thus CDF could become a novel, and effective anti-tumor agent for PC therapy.
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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.