ArticleLife (Basel, Switzerland)2021
Epigenetic Silencing of HER2 Expression during Epithelial-Mesenchymal Transition Leads to Trastuzumab Resistance in Breast Cancer.
Article in Life (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 23 citations in OpenAlex.
- miR-770-5p regulates KDM5B and links its nuclear localization to HER2 signaling in trastuzumab-resistant breast cancer.Molecular and cellular biochemistry · 2026Article
- Cycloastragenol overcomes trastuzumab resistance in HER2-positive breast cancer by regulating cell cycle and epithelial-mesenchymal transition through EZH2/PTEN/AKT pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Understanding and Overcoming Antibody-Drug Conjugate Resistance: Biological Mechanisms and Emerging Analytical Frameworks in Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Review
- ERBB2 amplification is a late event in the pathogenesis of high-grade endometrial carcinomas with heterogeneous HER2 expression.The Journal of pathology · 2026Article
- Review
- Tumor-Intrinsic PD-1 Regulatory Network Drives Lapatinib Resistance in HER2⁺ Breast Cancer: An Integrative Bioinformatics Analysis.Asian Pacific journal of cancer prevention : APJCP · 2026Article
- Antibody-Drug Conjugates in Breast Cancer: Therapeutic-Window Engineering, Tumor Heterogeneity, and Immunotherapy Combinations.Drug design, development and therapy · 2026Review
- Relationship Between Netrin-1 Staining and Neoadjuvant Treatment Response in HER2-Positive Locally Advanced Breast Cancer.Cancer management and research · 2026Article
- Epigenetic Regulation of Autophagy in Breast Cancer: Implications for Biomarker Discovery and Personalized Therapy.Cancer reports (Hoboken, N.J.) · 2025Review
- Natural and induced epithelial-mesenchymal transition results in epigenetic silencing of HER2 overexpression.Journal of mammary gland biology and neoplasia · 2025Article
- Intercellular signaling reinforces single-cell level phenotypic transitions and facilitates robust re-equilibrium of heterogeneous cancer cell populations.Cell communication and signaling : CCS · 2025Article
- Advancements in lung cancer: molecular insights, innovative therapies, and future prospects.Medical oncology (Northwood, London, England) · 2025Review
- Breaking Barriers in Breast Cancer: Multi-Targeted Therapeutic Insights.Mini reviews in medicinal chemistry · 2025Review
- Case report: Spatiotemporal HER2 heterogeneity in AFP-producing gastric cancer: navigating long-term survival with molecularly-guided therapy in a refractory case.Frontiers in immunology · 2025Article
- Decoding breast cancer treatment resistance through genetic, epigenetic, and immune-regulatory mechanisms: from molecular insights to translational perspectives.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Targeting ITGβ3 to Overcome Trastuzumab Resistance through Epithelial-Mesenchymal Transition Regulation in HER2-Positive Breast Cancer.International journal of molecular sciences · 2024Article
- Differential gene expression of immunity and inflammation genes in colorectal cancer using targeted RNA sequencing.Frontiers in oncology · 2023Article
- A PD-L1-targeting chimeric switch receptor enhances efficacy of CAR-T cell for pleural and peritoneal metastasis.Signal transduction and targeted therapy · 2022Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HER2 receptor tyrosine kinase (encoded by the ERBB2 gene) is overexpressed in approximately 25% of all breast cancer tumors (HER2-positive breast cancers). Resistance to HER2-targeting therapies is partially due to the loss of HER2 expression in tumor cells during treatment. However, little is known about the exact mechanism of HER2 downregulation in HER2-positive tumor cells. Here, by analyzing publicly available genomic data we investigate the hypothesis that epithelial-mesenchymal transition (EMT) abrogates HER2 expression by epigenetic silencing of the ERBB2 gene as a mechanism of acquired resistance to HER2-targeted therapies. As result, HER2 expression was found to be positively and negatively correlated with the expression of epithelial and mesenchymal phenotype marker genes, respectively. The ERBB2 chromatin of HER2-high epithelial-like breast cancer cells and HER2-low mesenchymal-like cells were found to be open/active and closed/inactive, respectively. Decreased HER2 expression was correlated with increased EMT phenotype, inactivated chromatin and lower response to lapatinib. We also found that induction of EMT in the HER2-positive breast cancer cell line BT474 resulted in downregulated HER2 expression and reduced trastuzumab binding. Our results suggest that ERBB2 gene silencing by epigenetic regulation during EMT may be a mechanism of de novo resistance of HER2-positive breast cancer cells to trastuzumab and lapatinib.
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.