ArticleJournal of experimental & clinical cancer research : CR2019
PYK2 promotes HER2-positive breast cancer invasion.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 65 citations in OpenAlex.
- FAK and Pyk2: Paralogous Kinases with Opposing Roles in Vasculogenic Mimicry in Triple-Negative Breast Cancer.International journal of molecular sciences · 2026Article
- Peripheral blood CD14 + monocytes in luminal breast carcinoma subtypes: in preliminary research and overview of candidate biomarker proteins.Scientific reports · 2026Article
- Exploring medicinal mechanism of baicalin in tumor microenvironment of melanoma via bioinformatic and in vitro study.Medical oncology (Northwood, London, England) · 2025Article
- Microwave dynamic therapy induces ferroptosis in colorectal cancer by targeting PTK2B to regulate STAT3-mediated GPX4 expression.Molecular biomedicine · 2025Article
- Targeting the hydrophobic pockets of FAK/PYK2 FAT domain: a highly effective inhibitory strategy suppressing tumor growth and eliminating metastasis.Cell communication and signaling : CCS · 2025Article
- PYK2 promotes cell proliferation and epithelial-mesenchymal transition in endometriosis by phosphorylating Snail1.Molecular medicine (Cambridge, Mass.) · 2025Article
- Exploring lipidomic profiles and their correlation with hormone receptor and HER2 status in breast cancer.Oncology letters · 2025Article
- Reduced Proline-Rich Tyrosine Kinase 2 Promotes Tumor Metastasis by Activating Epithelial-Mesenchymal Transition in Colorectal Cancer.Digestive diseases and sciences · 2024Article
- Integrin αVβ1-activated PYK2 promotes the progression of non-small-cell lung cancer via the STAT3-VGF axis.Cell communication and signaling : CCS · 2024Article
- A precision medicine approach to metabolic therapy for breast cancer in mice.Communications biology · 2022Article
- RETRACTED: Metformin and Breast Cancer: Where Are We Now?International journal of molecular sciences · 2022Review
- Systematic Identification of Genomic Markers for Guiding Iron Oxide Nanoparticles in Cervical Cancer Based on Translational Bioinformatics.International journal of nanomedicine · 2022Article
- RB1CC1 functions as a tumor-suppressing gene in renal cell carcinoma via suppression of PYK2 activity and disruption of TAZ-mediated PDL1 transcription activation.Cancer immunology, immunotherapy : CII · 2021Article
- Pyk2 level is a novel prognostic marker for patients with esophageal squamous cell carcinoma after radical surgery.Virchows Archiv : an international journal of pathology · 2021Article
- SDF1α/CXCR4 axis may be associated with the malignant progression of gastric cancer in the hypoxic tumor microenvironment.Oncology letters · 2021Article
- The histone H2B ubiquitin ligase RNF40 is required for HER2-driven mammary tumorigenesis.Cell death & disease · 2020Article
- Key Genes and Prognostic Analysis in HER2+ Breast Cancer.Technology in cancer research & treatmentArticle
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetformin, a biguanide, is one of the most commonly prescribed treatments for type 2 diabetes and has recently been recommended as a potential drug candidate for advanced cancer therapy. Although Metformin has antiproliferative and proapoptotic effects on breast cancer, the heterogenous nature of this disease affects the response to metformin leading to the activation of pro-invasive signalling pathways that are mediated by the focal adhesion kinase PYK2 in pure HER2 phenotype breast cancer.
methodsThe effect of metformin on different breast cancer cell lines, representing the molecular heterogenicity of the disease was investigated using in vitro proliferation and apoptosis assays. The activation of PYK2 by metformin in pure HER2 phenotype (HER2+/ER-/PR-) cell lines was investigated by microarrays, quantitative real time PCR and immunoblotting. Cell migration and invasion PYK2-mediated and in response to metformin were determined by wound healing and invasion assays using HER2+/ER-/PR- PYK2 knockdown cell lines. Proteomic analyses were used to determine the role of PYK2 in HER2+/ER-/PR- proliferative, migratory and invasive cellular pathways and in response to metformin. The association between PYK2 expression and HER2+/ER-/PR- patients' cancer-specific survival was investigated using bioinformatic analysis of PYK2 expression from patient gene expression profiles generated by the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) study. The effect of PYK2 and metformin on tumour initiation and invasion of HER2+/ER-/PR- breast cancer stem-like cells was performed using the in vitro stem cell proliferation and invasion assays.
resultsOur study showed for the first time that pure HER2 breast cancer cells are more resistant to metformin treatment when compared with the other breast cancer phenotypes. This drug resistance was associated with the activation of PTK2B/PYK2, a well-known mediator of signalling pathways involved in cell proliferation, migration and invasion. The role of PYK2 in promoting invasion of metformin resistant HER2 breast cancer cells was confirmed through investigating the effect of PYK2 knockdown and metformin on cell invasion and by proteomic analysis of associated cellular pathways. We also reveal a correlation between high level of expression of PYK2 and reduced survival in pure HER2 breast cancer patients. Moreover, we also report a role of PYK2 in tumour initiation and invasion-mediated by pure HER2 breast cancer stem-like cells. This was further confirmed by demonstrating a correlation between reduced survival in pure HER2 breast cancer patients and expression of PYK2 and the stem cell marker CD44.
conclusionsWe provide evidence of a PYK2-driven pro-invasive potential of metformin in pure HER2 cancer therapy and propose that metformin-based therapy should consider the molecular heterogeneity of breast cancer to prevent complications associated with cancer chemoresistance, invasion and recurrence in treated patients.
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