ArticleThe Journal of biological chemistry2013
The oncogene HER2/neu (ERBB2) requires the hypoxia-inducible factor HIF-1 for mammary tumor growth and anoikis resistance.
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 45 papers.
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Who cites it
45 citing papers in PubMed, 103 citations in OpenAlex.
- Anoikis in cancer: molecular mechanisms, resistance, and therapeutic strategies.Apoptosis : an international journal on programmed cell death · 2026Review
- Integrating network pharmacology, molecular dynamics, and in vitro assays to unveil the mechanism of costunolide against gastric cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Genome-Wide DNA Methylation Profiling Reveals Ancestry-Associated Epigenetic Reprogramming in Cervical Intraepithelial Neoplasia.International journal of molecular sciences · 2026Article
- Mesenchymal stem cell-derived exosomes improve vascular remodeling by inhibiting EGFR/ErbB2 heterodimerization in hypoxic pulmonary hypertension.Scientific reports · 2025Article
- Genome-wide selection signal analysis reveals the adaptability of Tibetan sheep to high altitudes.Frontiers in veterinary science · 2025Article
- EDI3 knockdown in ER-HER2+ breast cancer cells reduces tumor burden and improves survival in two mouse models of experimental metastasis.Breast cancer research : BCR · 2024Article
- HER2 Alterations in Non-Small Cell Lung Cancer: Biologico-Clinical Consequences and Interest in Therapeutic Strategies.Life (Basel, Switzerland) · 2023Review
- Anoikis resistance--protagonists of breast cancer cells survive and metastasize after ECM detachment.Cell communication and signaling : CCS · 2023Review
- Anoikis resistance in diffuse glioma: The potential therapeutic targets in the future.Frontiers in oncology · 2022Review
- The prognostic outcome of 'type 2 diabetes mellitus and breast cancer' association pivots on hypoxia-hyperglycemia axis.Cancer cell international · 2021Review
- Fibronectin assembly regulates lumen formation in breast acini.Journal of cellular biochemistry · 2021Article
- Novel Small Molecule Hsp90/Cdc37 Interface Inhibitors Indirectly Target K-Ras-Signaling.Cancers · 2021Article
- Mechanisms for Modulating Anoikis Resistance in Cancer and the Relevance of Metabolic Reprogramming.Frontiers in oncology · 2021Review
- Using sufficient direction factor model to analyze latent activities associated with breast cancer survival.Biometrics · 2020Article
- Upregulation of HIF1-α via an NF-κB/COX2 pathway confers proliferative dominance of HER2-negative ductal carcinoma in situ cells in response to inflammatory stimuli.Neoplasia (New York, N.Y.) · 2020Article
- Article
- HER2-mediated GLI2 stabilization promotes anoikis resistance and metastasis of breast cancer cells.Cancer letters · 2019Article
- Overexpression of HIF-1α contributes to melphalan resistance in multiple myeloma cells by activation of ERK1/2, Akt, and NF-κB.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Translational and HIF-1α-Dependent Metabolic Reprogramming Underpin Metabolic Plasticity and Responses to Kinase Inhibitors and Biguanides.Cell metabolism · 2018Article
- CAIX furthers tumour progression in the hypoxic tumour microenvironment of esophageal carcinoma and is a possible therapeutic target.Journal of enzyme inhibition and medicinal chemistry · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
ERBB2, a receptor tyrosine kinase amplified in breast cancer, is a well established regulator of tumor growth in vivo and anoikis resistance leading to disruption of architecture in three-dimensional mammary epithelial acinar structures in vitro. ERBB2 promotes anoikis resistance by maintaining signaling pathways and by rescuing metabolic defects and thus inhibiting accumulation of deleterious reactive oxygen species. Recent evidence suggests that hypoxia, via hypoxia-inducible factors (HIFs), can inhibit anoikis; thus, we hypothesized that HIF-1 may play a role in ERBB2-mediated anoikis resistance and oncogenesis. Indeed, tumors isolated from MMTV-Neu mice contain elevated HIF-1α levels and tumor cells created from MMTV-Neu mice harboring deletion of Hif1α alleles reduced primary tumor growth in vivo. ERBB2 overexpressing cancer cells stabilize HIF under normoxic conditions and require HIF-1 for ERBB2-mediated anchorage-independence, three-dimensional culture growth and anoikis resistance. HIF-1 reduction in ERBB2 cells was associated with induction of the pro-anoikis protein BIM and decreased ERK and AKT signaling during cell detachment. ERBB2-mediated inhibition of metabolic defects, including decreased reactive oxygen species generation in suspension, required HIF-1 expression that was critical for ERBB2-mediated oncogenesis. Gene expression profiling of hypoxic three-dimensional acinar structures identified a number of genes elevated in response to hypoxia that are known ERBB2 targets, suggesting that hypoxic conditions and ERBB2 overexpression share both phenotypic and genetic components via HIF-1 regulation. Thus, our data demonstrate that ERBB2 requires HIF-1 for tumor growth and suggest that HIF is a major downstream regulator of ERBB2 that protects cells from anoikis and metabolic stress caused by decreased matrix adhesion.
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