ArticleMolecular & cellular proteomics : MCP2013
Hypoxia modulates A431 cellular pathways association to tumor radioresistance and enhanced migration revealed by comprehensive proteomic and functional studies.
Article in Molecular & cellular proteomics : MCP, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 81 citations in OpenAlex.
- Plasma Proteomic Study in Pulmonary Arterial Hypertension Associated with Congenital Heart Diseases.Scientific reports · 2016Trial
- Angiogenesis and Resistance Mechanisms in Glioblastoma: Targeting Alternative Vascularization Pathways to Overcome Therapy Resistance.Current pharmaceutical design · 2026Review
- Evolving stratification and biomarker discovery in cancer research with technological advancement of proteomics: 35 years and counting.Bioscience reports · 2025Review
- Emerging PET Imaging Agents and Targeted Radioligand Therapy: A Review of Clinical Applications and Trials.Tomography (Ann Arbor, Mich.) · 2025Review
- Synthesis and evaluation of sulfonamide derivatives of quinoxaline 1,4-dioxides as carbonic anhydrase inhibitors.RSC advances · 2024Article
- Cellular Pre-Adaptation to the High OAntioxidants (Basel, Switzerland) · 2024Article
- The novel biomarkers for assessing clinical benefits of continuous renal replacement therapy in pediatric sepsis: a pilot study.Clinical proteomics · 2023Article
- Indoline-5-Sulfonamides: A Role of the Core in Inhibition of Cancer-Related Carbonic Anhydrases, Antiproliferative Activity and Circumventing of Multidrug Resistance.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Alterations of Lysine Acetylation Profile in Murine Skeletal Muscles Upon Exercise.Frontiers in aging neuroscience · 2022Article
- Identification of Novel Endogenous Controls for qPCR Normalization in SK-BR-3 Breast Cancer Cell Line.Genes · 2021Article
- Application of Advanced Mass Spectrometry-Based Proteomics to Study Hypoxia Driven Cancer Progression.Frontiers in oncology · 2021Review
- Proteomics Study Reveals the Anti-Depressive Mechanisms and the Compatibility Advantage of Chaihu-Shugan-San in a Rat Model of Chronic Unpredictable Mild Stress.Frontiers in pharmacology · 2021Article
- Proteomic Profiling of Lysine Acetylation Indicates Mitochondrial Dysfunction in the Hippocampus of Gut Microbiota-Absent Mice.Frontiers in molecular neuroscience · 2021Article
- Delayed postoperative radiotherapy might improve the long-term prognosis of locally advanced esophageal squamous cell carcinoma.Translational oncology · 2021Article
- Impact of hypoxia on DNA repair and genome integrity.Mutagenesis · 2020Review
- Delineation of hypoxia-induced proteome shifts in osteosarcoma cells with different metastatic propensities.Scientific reports · 2020Article
- Inside the hypoxic tumour: reprogramming of the DDR and radioresistance.Cell death discovery · 2020Review
- Further investigation of the characteristics and biological function of Eimeria tenella apical membrane antigen 1.Parasite (Paris, France) · 2020Article
- iTRAQ-based quantitative protein expression profiling of biomarkers in childhood B-cell and T-cell acute lymphoblastic leukemia.Cancer management and research · 2019Article
- iTRAQ-based comparative proteomic analysis of cells infected with Eimeria tenella sporozoites.Parasite (Paris, France) · 2019Article
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor hypoxia induces cancer cell angiogenesis, invasiveness, treatment resistance, and contributes to poor clinical outcome. However, the molecular mechanism by which tumor hypoxia exerts a coordinated effect on different molecular pathways to enhance tumor growth and survival and lead to poor clinical outcome is not fully understood. In this study, we attempt to elucidate the global protein expression and functional changes in A431 epithelial carcinoma cells induced by hypoxia and reoxygenation using iTRAQ quantitative proteomics and biochemical functional assays. Quantitative proteomics results showed that 4316 proteins were quantified with FDR<1%, in which over 1200 proteins were modulated >1.2 fold, and DNA repair, glycolysis, integrin, glycoprotein turnover, and STAT1 pathways were perturbed by hypoxia and reoxygenation-induced oxidative stress. For the first time, hypoxia was shown to up-regulate the nonhomologous end-joining pathway, which plays a central role in DNA repair of irradiated cells, thereby potentially contributing to the radioresistance of hypoxic A431 cells. The up-regulation of Ku70/Ku80 dimer, a key molecular complex in the nonhomologous end-joining pathway, was confirmed by Western blot and liquid chromatography/tandem mass spectrometry-MRM methods. Functional studies confirmed that up-regulation of glycolysis, integrin, glycoprotein synthesis, and down-regulation of STAT1 pathways during hypoxia enhanced metastastic activity of A431 cells. Migration of A431 cells was dramatically repressed by glycolysis inhibitor (2-Deoxy-d-glucose), glycoprotein synthesis inhibitor (1-Deoxynojirimycin Hydrochloride), and STAT1α overexpression that enhanced the integrin-mediated cell adhesion. These results revealed that hypoxia induced several biological processes involved in tumor migration and radioresistance and provided potential new targets for tumor therapy.
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