ArticleJournal of translational medicine2024
TCF12-regulated GRB7 facilitates the HER2+ breast cancer progression by activating Notch1 signaling pathway.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed.
- miR-770-5p regulates KDM5B and links its nuclear localization to HER2 signaling in trastuzumab-resistant breast cancer.Molecular and cellular biochemistry · 2026Article
- Transcript-aware rare genetic variant association analyses of cardiopulmonary traits in participants from the All of Us Research Program.Nature communications · 2026Article
- The Multifaceted Role of Extracellular Vesicles in Triple Negative Breast Cancer.International journal of molecular sciences · 2026Review
- SpaBiT: enhancing spatial transcriptomics resolution via bidirectional attention transformers.Bioinformatics (Oxford, England) · 2026Article
- Single-cell analysis reveals that NRG1/3-ERBB4 signaling affects metabolic reprogramming and immune escape in Wilms tumor.Biology direct · 2026Article
- TCF12-mediated transcriptional activation of CCDC34 is involved in the positive feedback of tumor-associated macrophages and EMT to promote LUSC.Cell biology and toxicology · 2026Article
- Nur77 Regulates the Phosphorylation of Smad3, Thereby Influencing Skeletal Muscle Fibrosis Caused by Obesity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Research Advances in Drug Resistance Mechanisms to Anti-HER2 Therapy in HER2-Positive Breast Cancer.Oncology research · 2026Review
- Review
- A Dynamic Contrast-Enhanced MRI-Based Vision Transformer Model for Distinguishing HER2-Zero, -Low, and -Positive Expression in Breast Cancer and Exploring Model Interpretability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Deep Learning Predicts Subtype Heterogeneity and Outcomes in Luminal A Breast Cancer Using Routinely Stained Whole-Slide Images.Cancer research communications · 2025Article
- Identification and Validation of circDOCK1/miR-138-5p/GRB7 Axis for Promoting Breast Cancer Progression.Breast cancer (Dove Medical Press) · 2024Article
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10 authors.
Funding
Abstract
backgroundHuman epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC), which accounts for approximately one-fifth of all BCs, are highly invasive with a high rate of recurrence and a poor prognosis. Several studies have shown that growth factor receptor-bound protein 7 (GRB7) might be a potential therapeutic target for tumor diagnosis and prognosis. Nevertheless, the role of GRB7 in HER2+ BC and its underlying mechanisms have not been fully elucidated. The aim of this study was to investigate the biological function and regulatory mechanism of GRB7 in HER2+ BC.
methodsBioinformatics analysis was performed using the TCGA, GEO and CancerSEA databases to evaluate the clinical significance of GRB7. RT quantitative PCR, western blot and immunofluorescence were conducted to assess the expression of GRB7 in BC cell lines and tissues. MTT, EdU, colony formation, wound healing, transwell, and xenograft assays were adopted to explore the biological function of GRB7 in HER2+ BC. RNA sequencing was performed to analyze the signaling pathways associated with GRB7 in SK-BR-3 cells after the cells were transfected with GRB7 siRNA. Chromatin immunoprecipitation analysis (ChIP) and luciferase reporter assay were employed to elucidate the potential molecular regulatory mechanisms of GRB7 in HER2+ BC.
resultsGRB7 was markedly upregulated and associated with poor prognosis in BC, especially in HER2+ BC. Overexpression of GRB7 increased the proliferation, migration, invasion, and colony formation of HER2+ BC cells, while depletion of GRB7 had the opposite effects in HER2+ BC cells and inhibited xenograft growth. ChIP-PCR and luciferase reporter assay revealed that TCF12 directly bound to the promoter of the GRB7 gene to promote its transcription. GRB7 facilitated HER2+ BC epithelial-mesenchymal transition (EMT) progression by interacting with Notch1 to activate Wnt/β-catenin pathways and other signaling (i.e., AKT, ERK). Moreover, forced GRB7 overexpression activated Wnt/β-catenin to promote EMT progression, and partially rescued the inhibition of HER2+ BC proliferation, migration and invasion induced by TCF12 silencing.
conclusionsOur work elucidates the oncogenic role of GRB7 in HER2+ BC, which could serve as a prognostic indicator and promising therapeutic target.
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