ArticleCancer cell international2013
Targeting PI3K/Akt represses Hypoxia inducible factor-1α activation and sensitizes Rhabdomyosarcoma and Ewing's sarcoma cells for apoptosis.
Article in Cancer cell international, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 99 citations in OpenAlex.
- The HIF-Mediated PI3K-AKT Signaling Pathway Is a Key Signaling Pathway Triggering Testicular Spermatogenic Disorders in Yaks with Cryptorchidism.Veterinary sciences · 2026Article
- A Review of HIF-1α-Mediated Integration of Metabolic Reprogramming, Mitochondrial Function, and PI3K/Akt-MAPK-Nrf2-NF-κB Signaling.Antioxidants (Basel, Switzerland) · 2026Review
- Exploring the genetic footprints of high altitude adapted humans and livestock.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Spatiotemporal Heterogeneity of Tumor Glucose Metabolism Reprogramming: From Single-Cell Mechanisms to Precision Interventions.International journal of molecular sciences · 2025Review
- CXCL6 Reshapes Lipid Metabolism and Induces Neutrophil Extracellular Trap Formation in Cholangiocarcinoma Progression and Immunotherapy Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Deciphering the role of circular RNAs in cancer progression under hypoxic conditions.Medical oncology (Northwood, London, England) · 2025Review
- Disrupting resistance: novel therapeutic approaches to combat multidrug resistance in fusion-negative rhabdomyosarcoma.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- CD73 contributes to the pathogenesis of fusion-negative rhabdomyosarcoma through the purinergic signaling pathway.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer.Frontiers in cell and developmental biology · 2024Review
- Targeted Inhibition of the PI3K/Akt/mTOR Signaling Axis: Potential for Sarcoma Therapy.Mini reviews in medicinal chemistry · 2024Review
- Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells - A potential contribution to the predictive, preventive, and personalized medicine.Journal of advanced research · 2024Review
- SIX1 and EWS/FLI1 co-regulate an anti-metastatic gene network in Ewing Sarcoma.Nature communications · 2023Article
- Hypoxia and HIFs in Ewing sarcoma: new perspectives on a multi-facetted relationship.Molecular cancer · 2023Review
- Transcriptome Analysis on Hepatopancreas Reveals the Metabolic Dysregulation Caused byBiology · 2023Article
- iPSCs derived from insulin resistant offspring of type 2 diabetic patients show increased oxidative stress and lactate secretion.Stem cell research & therapy · 2022Article
- How Phosphofructokinase-1 Promotes PI3K and YAP/TAZ in Cancer: Therapeutic Perspectives.Cancers · 2022Article
- Lactate promotes the growth of patient-derived organoids from hepatopancreatobiliary cancers via ENO1/HIF1α pathway and does not affect their drug sensitivities.Cell death discovery · 2022Article
- Splice-switching of the insulin receptor pre-mRNA alleviates tumorigenic hallmarks in rhabdomyosarcoma.NPJ precision oncology · 2022Article
- Proton pump inhibitors and sensitization of cancer cells to radiation therapy.Frontiers in oncology · 2022Review
- Circulating lncRNAs HIF1A-AS2 and LINLK-A: Role and Relation to Hypoxia-Inducible Factor-1α in Cerebral Stroke Patients.Molecular neurobiology · 2021Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHypoxia inducible factor-1 α (HIF-1α) has been identified as an important novel target in apoptosis resistance of pediatric tumors such as Rhabdomyosarcoma (RMS) and Ewing's sarcoma (ES). Evidence suggests that PI3K/Akt signaling plays a role in regulation of HIF-1α activation as well as apoptosis resistance in various adult tumors. However the relevance of PI3K/Akt signaling in HIF-1bα activation and apoptosis resistance in childhood tumors has not been addressed yet. Thus, this study was to investigate whether PI3K/Akt signaling is involved in hypoxia induced activation of HIF-1α as well as in resistance to hypoxia-induced apoptosis in childhood tumors such as RMS and ES.
methodsConstitutive activation of PI3K/Akt signaling was analyzed by Western blotting. Hypoxic activation of HIF-1α was determined by Western Blot analysis and electrophoretic mobility shift assay. Apoptosis was determined by flow cytometric analysis of the propidium iodine stained nuclei of cells treated with PI3K inhibitor LY294002 in combination with either TNF-related apoptosis-inducing ligand (TRAIL) or doxorubicin.
resultsThis study demonstrated that PI3K/Akt signaling was constitutively activated in RMS and ES cell lines, A204 and A673, respectively. Targeting PI3K/Akt signaling by the inhibitor LY294002 (30 μM) significantly decreased the protein expression as well as DNA binding activity of HIF-1α and restored the apoptosis-inducing ability of cells in hypoxia Additionally, pretreatment with LY294002 sensitized A204 and A673 cells to TRAIL or doxorubicin induced apoptosis under hypoxia.
conclusionThese results suggest that the constitutively active PI3K/Akt signaling contributes to hypoxic activation of HIF-1α as well as HIF1α-mediated apoptosis resistance in RMS and ES cells under hypoxia.
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