ArticlePloS one2013
Spontaneous epithelial-mesenchymal transition and resistance to HER-2-targeted therapies in HER-2-positive luminal breast cancer.
Article in PloS one, 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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Who cites it
40 citing papers in PubMed, 70 citations in OpenAlex.
- EMT and cancer: what clinicians should know.Nature reviews. Clinical oncology · 2025Review
- Increased prevalence of hybrid epithelial/mesenchymal state and enhanced phenotypic heterogeneity in basal breast cancer.iScience · 2024Article
- iGenSig-Rx: an integral genomic signature based white-box tool for modeling cancer therapeutic responses using multi-omics data.BMC bioinformatics · 2024Article
- Grainyhead-like-2, an epithelial master programmer, promotes interferon induction and suppresses breast cancer recurrence.Molecular immunology · 2024Article
- Proteomic Assessment of SKBR3/HER2+ Breast Cancer Cellular Response to Lapatinib and Investigational Ipatasertib Kinase Inhibitors.bioRxiv : the preprint server for biology · 2024Article
- An inflamed tumor cell subpopulation promotes chemotherapy resistance in triple negative breast cancer.Scientific reports · 2024Article
- Update on Epithelial-Mesenchymal Plasticity in Cancer Progression.Annual review of pathology · 2024Review
- Proteomic assessment of SKBR3/HER2+ breast cancer cellular response to Lapatinib and investigational Ipatasertib kinase inhibitors.Frontiers in pharmacology · 2024Article
- iGenSig-Rx: an integral genomic signature based white-box tool for modeling cancer therapeutic responses using multi-omics data.Research square · 2023Article
- Identification and panoramic analysis of drug response-related genes in triple negative breast cancer using as an example NVP-BEZ235.Scientific reports · 2023Article
- Integrin αvβ3 Is a Master Regulator of Resistance to TKI-Induced Ferroptosis in HER2-Positive Breast Cancer.Cancers · 2023Article
- Review
- Inhibiting Cyclin-Dependent Kinase 6 by Taurine: Implications in Anticancer Therapeutics.ACS omega · 2022Article
- Presence of spontaneous epithelial-mesenchymal plasticity in esophageal cancer.Biochemistry and biophysics reports · 2022Article
- [Metformin inhibits proliferation and promotes apoptosis of HER-2 positive breast cancer cells possibly through the Hippo-YAP pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- circRNAs in drug resistance of breast cancer.Oncology research · 2022Review
- Review
- Epigenetic Silencing of HER2 Expression during Epithelial-Mesenchymal Transition Leads to Trastuzumab Resistance in Breast Cancer.Life (Basel, Switzerland) · 2021Article
- The pan-cancer landscape of crosstalk between epithelial-mesenchymal transition and immune evasion relevant to prognosis and immunotherapy response.NPJ precision oncology · 2021Article
- 5-AZA-dC induces epigenetic changes associated with modified glycosylation of secreted glycoproteins and increased EMT and migration in chemo-sensitive cancer cells.Clinical epigenetics · 2021Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to trastuzumab, a rationally designed HER-2-targeting antibody, remains a major hurdle in the management of HER-2-positive breast cancer. Preclinical studies suggest the mechanisms of trastuzumab resistance are numerous. Unfortunately, the majority of these studies are based around HER-2-positive (HER-2+) luminal cell lines. The role of epithelial to mesenchymal transition (EMT), a genetic program that confers a basal phenotype, may represent a novel mechanism of escape for HER-2+ luminal cells from trastuzumab treatment. Here we investigated this possibility using a model of clonal selection in HER-2+ luminal breast cancer cells. Following a random isolation and expansion of "colony clusters" from SKBR-3 cell lines, several colony clusters underwent a spontaneous EMT in-vitro. In addition to expression of conventional EMT markers, all mesenchymal colony clusters displayed a predominant CD44+/CD24- phenotype with decreased HER-2 expression and elevated levels of a β1-integrin isoform with a high degree of N-glycosylation. Treatment with a β1-integrin function-blocking antibody, AIIB2, preferentially decreased the N-glycosylated form of β1-integrin, impaired mammosphere formation and restored epithelial phenotype in mesenchymal colony clusters. Using this model we provide the first clear evidence that resistance to trastuzumab (and lapatinib) can occur spontaneously as HER-2+ cells shift from a luminal to a basal/mesenchymal phenotype following EMT. While the major determinant of trastuzumab resistance in mesenchymal colony clusters is likely the down regulation of the HER-2 protein, our evidence suggests that multiple factors may contribute, including expression of N-glycosylated β1-integrin.
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Registered trials
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