ArticleThe Journal of biological chemistry2006
Cross-talk between epidermal growth factor receptor and hypoxia-inducible factor-1alpha signal pathways increases resistance to apoptosis by up-regulating survivin gene expression.
Article in The Journal of biological chemistry, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
140 citing papers in PubMed, 3 syntheses or guidelines pooled it, 294 citations in OpenAlex.
- Clinicopathological and prognostic significance of hypoxia-inducible factor-1 alpha in lung cancer: a systematic review with meta-analysis.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2016Pooled it
- Association between survivin -31G>C polymorphism and cancer risk: meta-analysis of 29 studies.Journal of cancer research and clinical oncology · 2014Pooled it
- Association between survivin -31G > C promoter polymorphism and cancer risk: a meta-analysis.European journal of human genetics : EJHG · 2012Pooled it
- The role of hypoxia-inducible factors in myocardial ischaemia-reperfusion injury and cardioprotection.Nature reviews. Cardiology · 2026Review
- Interplay between nuclear survivin and the PRC2 complex and its impact on H3K27me3-directed transcriptional repression.Journal of cell science · 2026Article
- HIF-1α siRNA Enhances the Efficacy of Erlotinib in Non-small Cell Lung Cancer: A Novel Strategy to Reverse Hypoxia-Induced Drug Resistance.Drugs in R&D · 2026Article
- Mosaic partial epidermal reprogramming remodels neighbors and niches to refine skin homeostasis and repair.Nature communications · 2026Article
- Synergistic Targeting of EGFR, ESR1, BCL2, and TP53 Pathways: A Multi-Pronged Approach for Advanced Breast Cancer Therapy.Current cancer drug targets · 2026Review
- Stimulator of interferon genes (STING) immunohistochemical expression in fumarate hydratase-deficient renal cell carcinoma: biological and potential predictive implications.Virchows Archiv : an international journal of pathology · 2025Article
- Targeting metabolic and epigenetic reprogramming in metastatic fumarate hydratase-deficient renal cell carcinoma.Clinical & experimental metastasis · 2025Review
- Human Mesenchymal Stromal Cells Derived from Different Tissues Show Similar Profiles of c-ErbB Receptor Family Expression at the mRNA and Protein Levels.International journal of molecular sciences · 2025Article
- Whole methylomes reveal high-altitude-associated methylation at hypoxia and pigmentation genes in South American Indigenous populations.Environmental epigenetics · 2025Article
- Survivin in lung cancer: a potential target for therapy and prevention-a narrative review.Translational lung cancer research · 2024Review
- A combined opposite targeting of p110δ PI3K and RhoA abrogates skin cancer.Communications biology · 2024Article
- Anti-BIRC5 autoantibody serves as a valuable biomarker for diagnosing AFP-negative hepatocellular carcinoma.PeerJ · 2024Article
- Unmasking the enigma: A case of Fumarate Hydratase-deficient renal cell carcinoma.International journal of surgery case reports · 2023Article
- Outcome benefits of bevacizumab biosimilar (SIBP04) combined with carboplatin and paclitaxel in advanced non-squamous non-small-cell lung cancer patients with EGFR mutation: subgroup analysis of a prospective, randomized phase III clinical trial.Journal of cancer research and clinical oncology · 2023Article
- Role of Interleukin(IL)-6 in NK Activity to Hypoxic-Induced Highly Invasive Hepatocellular Carcinoma(HCC) Cells.Journal of microbiology and biotechnology · 2023Article
- In Silico Evaluation of HN-N07 Small Molecule as an Inhibitor of Angiogenesis and Lymphangiogenesis Oncogenic Signatures in Non-Small Cell Lung Cancer.Biomedicines · 2023Article
- Role of hypoxia-inducible factor-1α and survivin in breast cancer recurrence and prognosis.Heliyon · 2023Article
80 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
6 authors at 4 institutions in 1 country.
Funding
Abstract
Although increasing evidence supports a link between epidermal growth factor receptor (EGFR) signaling and resistance to apoptosis, the mechanism by which the EGFR signaling pathway inhibits apoptosis is not well understood. In this study, we found that epidermal growth factor (EGF) stimulation increased the level of expression of the inhibitor of apoptosis protein survivin in breast cancer cells but not in normal mammary epithelial cells. We further demonstrated that activation of survivin gene expression is mediated by oxygen-independent hypoxia-inducible factor (HIF)-1alpha up-regulation in EGF-treated cancer cells. EGFR signaling activated the phosphoinositide 3-kinase/AKT pathway, subsequently increasing the level of HIF-1alpha under normoxic conditions. HIF-1alpha then activated survivin gene transcription through direct binding to the survivin promoter. Furthermore, we found that overexpression of HIF-1alpha small interfering RNA blocks EGF-induced survivin gene up-regulation and increases apoptosis induced by the chemotherapy drug docetaxel. However, transfection of a plasmid expressing HIF-1alpha gene activates survivin gene expression and reduces the apoptotic response. Our results demonstrate a novel pathway for EGFR signaling-mediated apoptosis resistance in human cancer cells. Although the role of HIF-1alpha in regulating cell survival under hypoxic conditions has been studied extensively, our results show that normoxic breast cancer cells utilize cross-talk between EGFR signals and HIF-1alpha to up-regulate the anti-apoptotic survivin gene, providing a strong rationale for the targeting of HIF-1alpha as a therapeutic approach for both hypoxic and normoxic tumor cells. Understanding key molecular events in EGFR signaling-induced apoptosis resistance should provide new information for the development of novel therapeutic agents targeting EGFR, HIF-1alpha, and/or survivin.
Indexed as
Identifiers
What OpenQuestion holds
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.