ArticleBreast cancer research : BCR2015
Upregulation of EGFR signaling is correlated with tumor stroma remodeling and tumor recurrence in FGFR1-driven breast cancer.
Article in Breast cancer research : BCR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 71 citations in OpenAlex.
- Distinct Oxidative Stress Adaptations Driven by the Overexpression of miR-526b, miR-655, and COX-2 in Breast Cancer.International journal of molecular sciences · 2025Article
- Fibroblast growth factor receptor signaling modulates cholesterol storage in a SOAT1-dependent manner to promote mammary tumor cell invasion.Breast cancer research : BCR · 2025Article
- Testosterone/androgen receptor antagonizes immobility-induced muscle atrophy through Inhibition of myostatin transcription and inflammation in mice.Scientific reports · 2025Article
- Therapies targeting triple-negative breast cancer: a perspective on anti-FGFR.Frontiers in oncology · 2024Review
- Receptor tyrosine kinases in breast cancer treatment: unraveling the potential.American journal of cancer research · 2024Review
- Dormancy in Breast Cancer.Cold Spring Harbor perspectives in medicine · 2023Review
- Whole exome and transcriptome analysis revealed the activation of ERK and Akt signaling pathway in canine histiocytic sarcoma.Scientific reports · 2023Article
- Unleashing the potential of combining FGFR inhibitor and immune checkpoint blockade for FGF/FGFR signaling in tumor microenvironment.Molecular cancer · 2023Review
- Ion channel geneFrontiers in oncology · 2023Article
- Dual-targeted near-infrared photoimmunotherapy for esophageal cancer and cancer-associated fibroblasts in the tumor microenvironment.Scientific reports · 2022Article
- Single-Cell Analysis Unveils the Role of the Tumor Immune Microenvironment and Notch Signaling in Dormant Minimal Residual Disease.Cancer research · 2022Article
- Comprehensive analysis of the prognostic value and immune infiltration ofFrontiers in oncology · 2022Article
- Upregulation of the ErbB family by EZH2 in hepatocellular carcinoma confers resistance to FGFR inhibitor.Journal of cancer research and clinical oncology · 2021Article
- FGFR Inhibitors in Oncology: Insight on the Management of Toxicities in Clinical Practice.Cancers · 2021Review
- Reverse-Phase Protein Array: Technology, Application, Data Processing, and Integration.Journal of biomolecular techniques : JBT · 2021Article
- Constitutive activation of mitogen-activated protein kinase kinase (MEK1) in ileal enterocytes leads to dysplasia and a predisposition to cancer.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- MET-Pyk2 Axis Mediates Acquired Resistance to FGFR Inhibition in Cancer Cells.Frontiers in oncology · 2021Article
- Autophagy and Cancer Dormancy.Frontiers in oncology · 2021Review
- Therapeutically Targeting Cancers That Overexpress FOXC1: A Transcriptional Driver of Cell Plasticity, Partial EMT, and Cancer Metastasis.Frontiers in oncology · 2021Review
- Rab8 and Rabin8-Mediated Tumor Formation by Hyperactivated EGFR Signaling via FGFR Signaling.International journal of molecular sciences · 2020Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
introductionDespite advances in early detection and adjuvant targeted therapies, breast cancer is still the second most common cause of cancer mortality among women. Tumor recurrence is one of the major contributors to breast cancer mortality. However, the mechanisms underlying this process are not completely understood. In this study, we investigated the mechanisms of tumor dormancy and recurrence in a preclinical mouse model of breast cancer.
methodsTo elucidate the mechanisms driving tumor recurrence, we employed a transplantable Wnt1/inducible fibroblast growth factor receptor (FGFR) 1 mouse mammary tumor model and utilized an FGFR specific inhibitor, BGJ398, to study the recurrence after treatment. Histological staining was performed to analyze the residual tumor cells and tumor stroma. Reverse phase protein array was performed to compare primary and recurrent tumors to investigate the molecular mechanisms leading to tumor recurrence.
resultsTreatment with BGJ398 resulted in rapid tumor regression, leaving a nonpalpable mass of dormant tumor cells organized into a luminal and basal epithelial layer similar to the normal mammary gland, but surrounded by dense stroma with markedly reduced levels of myeloid-derived tumor suppressor cells (MDSCs) and decreased tumor vasculature. Following cessation of treatment the tumors recurred over a period of 1 to 4 months. The recurrent tumors displayed dense stroma with increased collagen, tenascin-C expression, and MDSC infiltration. Activation of the epidermal growth factor receptor (EGFR) pathway was observed in recurrent tumors, and inhibition of EGFR with lapatinib in combination with BGJ398 resulted in a significant delay in tumor recurrence accompanied by reduced stroma, yet there was no difference observed in initial tumor regression between the groups treated with BGJ398 alone or in combination with lapatinib.
conclusionThese studies have revealed a correlation between tumor recurrence and changes of stromal microenvironment accompanied by altered EGFR signaling.
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