ArticlePloS one2011
PI3K and ERK-induced Rac1 activation mediates hypoxia-induced HIF-1α expression in MCF-7 breast cancer cells.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 101 citations in OpenAlex.
- Induction of protective proteins is fundamental to hyperbaric oxygen preconditioning.Frontiers in cell and developmental biology · 2026Review
- Rac1 in gastric cancer: a molecular driver of invasion, EMT, and therapeutic resistance.Journal of translational medicine · 2025Review
- Review
- Hypoxia Modulates Transmembrane Prostatic Acid Phosphatase (TM-PAP) in MCF-7 Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Review
- Adipose Tissue Hypoxia in Obesity: Clinical Reappraisal of Hypoxia Hypothesis.Advances in experimental medicine and biology · 2024Review
- Review
- The CD146-HIF-1α axis regulates epithelial cell migration and alveolar maturation in a mouse model of bronchopulmonary dysplasia.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Macrophage Motility in Wound Healing Is Regulated by HIF-1α via S1P Signaling.International journal of molecular sciences · 2021Review
- Hypoxia-induced alternative splicing in human diseases: the pledge, the turn, and the prestige.Cellular and molecular life sciences : CMLS · 2021Review
- Article
- VISTA: A Mediator of Quiescence and a Promising Target in Cancer Immunotherapy.Trends in immunology · 2021Review
- Cross-Talk between Oxidative Stress and mOxidative medicine and cellular longevity · 2021Review
- Contribution of Oxidative Stress to HIF-1-Mediated Profibrotic Changes during the Kidney Damage.Oxidative medicine and cellular longevity · 2021Review
- The ZNF750-RAC1 axis as potential prognostic factor for breast cancer.Cell death discovery · 2020Article
- Chrysin Inhibits High Glucose-Induced Migration on Chorioretinal Endothelial Cells via VEGF and VEGFR Down-Regulation.International journal of molecular sciences · 2020Article
- The Rho GTPase RAC1 in Osteoblasts Controls Their Function.International journal of molecular sciences · 2020Article
- Stress-Sensitive Protein Rac1 and Its Involvement in Neurodevelopmental Disorders.Neural plasticity · 2020Review
- Article
- Sphingolipids in Obesity and Correlated Co-Morbidities: The Contribution of Gender, Age and Environment.International journal of molecular sciences · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHypoxia-inducible factor 1 (HIF-1α) expression induced by hypoxia plays a critical role in promoting tumor angiogenesis and metastasis. However, the molecular mechanisms underlying the induction of HIF-1α in tumor cells remain unknown. METHODOLOGY/PRINCIPAL
findingsIn this study, we reported that hypoxia could induce HIF-1α and VEGF expression accompanied by Rac1 activation in MCF-7 breast cancer cells. Blockade of Rac1 activation with ectopic expression of an inactive mutant form of Rac1 (T17N) or Rac1 siRNA downregulated hypoxia-induced HIF-1α and VEGF expression. Furthermore, Hypoxia increased PI3K and ERK signaling activity. Both PI3K inhibitor LY294002 and ERK inhibitor U0126 suppressed hypoxia-induced Rac1 activation as well as HIF-1α expression. Moreover, hypoxia treatment resulted in a remarkable production of reactive oxygen species (ROS). N-acetyl-L-cysteine, a scavenger of ROS, inhibited hypoxia-induced ROS generation, PI3K, ERK and Rac1 activation as well as HIF-1α expression. CONCLUSIONS/SIGNIFICANCE: Taken together, our study demonstrated that hypoxia-induced HIF-1α expression involves a cascade of signaling events including ROS generation, activation of PI3K and ERK signaling, and subsequent activation of Rac1.
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