ArticleThe Journal of biological chemistry2013
Hypoxia-inducible factor-1α (HIF-1α) promotes cap-dependent translation of selective mRNAs through up-regulating initiation factor eIF4E1 in breast cancer cells under hypoxia conditions.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 62 citations in OpenAlex.
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- Living on the Edge: ROS Homeostasis in Cancer Cells and Its Potential as a Therapeutic Target.Antioxidants (Basel, Switzerland) · 2025Review
- Prognostic value of circadian rhythm-associated genes in breast cancer.World journal of surgical oncology · 2025Article
- Non-canonical mRNA translation initiation in cell stress and cancer.NAR cancer · 2024Review
- Visfatin Facilitates VEGF-D-Induced Lymphangiogenesis through Activating HIF-1α and Suppressing miR-2277-3p in Human Chondrosarcoma.International journal of molecular sciences · 2024Article
- A Breast Cancer Stem Active Cobalt(III)-Cyclam Complex Containing Flufenamic Acid with Immunogenic Potential.Angewandte Chemie (International ed. in English) · 2024Article
- The Role of the Hypoxia-Related Unfolded Protein Response (UPR) in the Tumor Microenvironment.Cancers · 2022Review
- Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis.Cell reports · 2021Article
- Deep computational analysis details dysregulation of eukaryotic translation initiation complex eIF4F in human cancers.Cell systems · 2021Article
- Synthetic mRNAs; Their Analogue Caps and Contribution to Disease.Diseases (Basel, Switzerland) · 2021Review
- Cancer Plasticity: The Role of mRNA Translation.Trends in cancer · 2021Review
- Hypoxia re-programs 2'-O-Me modifications on ribosomal RNA.iScience · 2021Article
- Impact of Eukaryotic Translation Initiation Factors on Breast Cancer: Still Much to Investigate.Cancers · 2020Review
- A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism.Nature communications · 2020Article
- DEAD Box Protein Family Member DDX28 Is a Negative Regulator of Hypoxia-Inducible Factor 2α- and Eukaryotic Initiation Factor 4E2-Directed Hypoxic Translation.Molecular and cellular biology · 2020Article
- The Effect of MicroRNA-101 on Angiogenesis of Human Umbilical Vein Endothelial Cells during Hypoxia and in Mice with Myocardial Infarction.BioMed research international · 2020Article
- Unfolded protein response (UPR) integrated signaling networks determine cell fate during hypoxia.Cellular & molecular biology letters · 2020Review
- Translational Control in Cancer.Cold Spring Harbor perspectives in biology · 2019Review
- Mesenchymal stem cells of Systemic Sclerosis patients, derived from different sources, show a profibrotic microRNA profiling.Scientific reports · 2019Article
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4 authors at 1 institution in 1 country.
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Abstract
Hypoxia promotes tumor evolution and metastasis, and hypoxia-inducible factor-1α (HIF-1α) is a key regulator of hypoxia-related cellular processes in cancer. The eIF4E translation initiation factors, eIF4E1, eIF4E2, and eIF4E3, are essential for translation initiation. However, whether and how HIF-1α affects cap-dependent translation through eIF4Es in hypoxic cancer cells has been unknown. Here, we report that HIF-1α promoted cap-dependent translation of selective mRNAs through up-regulation of eIF4E1 in hypoxic breast cancer cells. Hypoxia-promoted breast cancer tumorsphere growth was HIF-1α-dependent. We found that eIF4E1, not eIF4E2 or eIF4E3, is the dominant eIF4E family member in breast cancer cells under both normoxia and hypoxia conditions. eIF4E3 expression was largely sequestered in breast cancer cells at normoxia and hypoxia. Hypoxia up-regulated the expression of eIF4E1 and eIF4E2, but only eIF4E1 expression was HIF-1α-dependent. In hypoxic cancer cells, HIF-1α-up-regulated eIF4E1 enhanced cap-dependent translation of a subset of mRNAs encoding proteins important for breast cancer cell mammosphere growth. In searching for correlations, we discovered that human eIF4E1 promoter harbors multiple potential hypoxia response elements. Furthermore, using chromatin immunoprecipitation (ChIP) and luciferase and point mutation assays, we found that HIF-1α utilized hypoxia response elements in the human eIF4E1 proximal promoter region to activate eIF4E1 expression. Our study suggests that HIF-1α promotes cap-dependent translation of selective mRNAs through up-regulating eIF4E1, which contributes to tumorsphere growth of breast cancer cells at hypoxia. The data shown provide new insights into protein synthesis mechanisms in cancer cells at low oxygen levels.
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