ArticleMolecular and cellular biology2001
HER2 (neu) signaling increases the rate of hypoxia-inducible factor 1alpha (HIF-1alpha) synthesis: novel mechanism for HIF-1-mediated vascular endothelial growth factor expression.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01191697 (Phase II Trial of CAPOX, Bevacizumab and Trastuzumab for Patients With HER2-Positive Metastatic Esophagogastric Cancer), which is not on this map. Cited by 459 papers.
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.
Phase II Trial of CAPOX, Bevacizumab and Trastuzumab for Patients With HER2-Positive Metastatic Esophagogastric Cancer
Who cites it
459 citing papers in PubMed, 1,245 citations in OpenAlex.
- Clinical outcomes and ctDNA correlates for CAPOX BETR: a phase II trial of capecitabine, oxaliplatin, bevacizumab, trastuzumab in previously untreated advanced HER2+ gastroesophageal adenocarcinoma.Nature communications · 2024Trial
- From barrier to trigger: leveraging tumor hypoxia for precise control of CAR-T cell activity.Molecular biology reports · 2026Review
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Normoxic HIFα-mediated metabolic rewiring in cancer as a novel therapeutic target of tumor heterogeneity.Cancer & metabolism · 2026Article
- Vascular Endothelial Growth Factor/Angiopoietin-2 Bispecific Antibody-Induced Vascular Normalization: From Basic Mechanisms to Therapeutic Applications in Breast Cancer.Immunity, inflammation and disease · 2026Review
- Deciphering the interplay between hypoxia, angiogenesis, and endoplasmic reticulum stress in carcinogenesis: A narrative review.World journal of experimental medicine · 2026Review
- Individualized prediction of brain metastasis risk in patients with breast cancer.Journal of neuro-oncology · 2026Article
- Hypoxia Signaling and Non-Coding RNAs: Regulatory Networks and Therapeutic Implications in Breast Cancer.Current issues in molecular biology · 2026Review
- Review
- Exploring the genetic footprints of high altitude adapted humans and livestock.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Biological Regulation of HIF-1α and Its Role in Therapeutic Angiogenesis for Treatment of Ischemic Cardiovascular Disease.International journal of molecular sciences · 2025Review
- Vascular endothelial generating factor pathway in ovarian cancer.Journal of ovarian research · 2025Review
- Impaired natural killer cell migration in HIV-infected individuals is caused by TIGIT-mediated inhibition of HIF-1α-dependent glycolysis.Cell death & disease · 2025Article
- ECD co-operates with ERBB2 to promote tumorigenesis through upregulation of unfolded protein response and glycolysis.Cancer letters · 2025Article
- Gut Microbiota and Bacterial Extracellular Vesicles: Emerging Roles in Myocardial Remodelling and Cardiac Health.Journal of extracellular biology · 2025Review
- Sialylated IgG expressed in triple-negative breast cancer cells promotes cancer progression by promoting glycolysis.Breast cancer research : BCR · 2025Article
- Unveiling GBE1 as a hypoxia-related prognostic gene with significant impact on immune cell infiltration in HER2-enriched breast cancer.Discover oncology · 2025Article
- Ephedrine Attenuates LPS-Induced Acute Lung Injury in Mice by Inhibiting OTUB1 and Promoting K48 Ubiquitination of HIF1α.Journal of cellular and molecular medicine · 2025Article
- 5-Aminolaevulinic Acid-Mediated Photodynamic Therapy Combined with Tirapazamine Enhances Efficacy in Ovarian Cancer.Biomedicines · 2025Article
- Hypoxia-inducible transcription factors: architects of tumorigenesis and targets for anticancer drug discovery.Transcription · 2025Review
399 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
5 authors at 2 institutions in 1 country.
Funding
Abstract
Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator composed of HIF-1alpha and HIF-1beta subunits. Several dozen HIF-1 targets are known, including the gene encoding vascular endothelial growth factor (VEGF). Under hypoxic conditions, HIF-1alpha expression increases as a result of decreased ubiquitination and degradation. The tumor suppressors VHL (von Hippel-Lindau protein) and p53 target HIF-1alpha for ubiquitination such that their inactivation in tumor cells increases the half-life of HIF-1alpha. Increased phosphatidylinositol 3-kinase (PI3K) and AKT or decreased PTEN activity in prostate cancer cells also increases HIF-1alpha expression by an undefined mechanism. In breast cancer, increased activity of the HER2 (also known as neu) receptor tyrosine kinase is associated with increased tumor grade, chemotherapy resistance, and decreased patient survival. HER2 has also been implicated as an inducer of VEGF expression. Here we demonstrate that HER2 signaling induced by overexpression in mouse 3T3 cells or heregulin stimulation of human MCF-7 breast cancer cells results in increased HIF-1alpha protein and VEGF mRNA expression that is dependent upon activity of PI3K, AKT (also known as protein kinase B), and the downstream kinase FRAP (FKBP-rapamycin-associated protein). In contrast to other inducers of HIF-1 expression, heregulin stimulation does not affect the half-life of HIF-1alpha but instead stimulates HIF-1alpha synthesis in a rapamycin-dependent manner. The 5'-untranslated region of HIF-1alpha mRNA directs heregulin-inducible expression of a heterologous protein. These data provide a molecular basis for VEGF induction and tumor angiogenesis by heregulin-HER2 signaling and establish a novel mechanism for the regulation of HIF-1alpha expression.
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.