ArticleBreast cancer research : BCR2019
Absence of integrin α3β1 promotes the progression of HER2-driven breast cancer in vivo.
Article in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 23 citations in OpenAlex.
- Integrin α3Cancer pathogenesis and therapy · 2026Article
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- Laminin Receptors in Peripheral Tissues: Functions Revealed by Analysis of Knockout Mice.The American journal of pathology · 2025Review
- Interplay of integrins and selectins in metastasis.Molecular oncology · 2025Review
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- FBLN2 is associated with basal cell markers Krt14 and ITGB1 in mouse mammary epithelial cells and has a preferential expression in molecular subtypes of human breast cancer.Breast cancer research and treatment · 2024Article
- The epidermal integrin-mediated secretome regulates the skin microenvironment during tumorigenesis and repair.Matrix biology : journal of the International Society for Matrix Biology · 2024Review
- Roles for epithelial integrin α3β1 in regulation of the microenvironment during normal and pathological tissue remodeling.American journal of physiology. Cell physiology · 2024Review
- Targeting collagen XVIII improves the efficiency of ErbB inhibitors in breast cancer models.The Journal of clinical investigation · 2023Article
- Review
- Understanding the role of integrins in breast cancer invasion, metastasis, angiogenesis, and drug resistance.Oncogene · 2021Review
- Expression and Gene Regulation Network of Adenosine Receptor A2B in Lung Adenocarcinoma: A Potential Diagnostic and Prognostic Biomarker.Frontiers in molecular biosciences · 2021Article
- Loss of the nuclear Wnt pathway effector TCF7L2 promotes migration and invasion of human colorectal cancer cells.Oncogene · 2020Article
- IntegrinB5 upregulated by HER2 in gastric cancer: a promising biomarker for liver metastasis.Annals of translational medicine · 2020Article
- Review
- The Biological Functions and Clinical Applications of Integrins in Cancers.Frontiers in pharmacology · 2020Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHER2-driven breast cancer is correlated with poor prognosis, especially during its later stages. Numerous studies have shown the importance of the integrin α3β1 during the initiation and progression of breast cancer; however, its role in this disease is complex and often opposite during different stages and in different types of tumors. In this study, we aim to elucidate the role of integrin α3β1 in a genetically engineered mouse model of HER2-driven mammary tumorigenesis.
methodsTo investigate the role of α3β1 in HER2-driven tumorigenesis in vivo, we generated a HER2-driven MMTV-cNeu mouse model of mammary tumorigenesis with targeted deletion of Itga3 (Itga3 KO mice). We have further used several established triple-negative and HER2-overexpressing human mammary carcinoma cell lines and generated ITGA3-knockout cells to investigate the role of α3β1 in vitro. Invasion of cells was assessed using Matrigel- and Matrigel/collagen I-coated Transwell assays under static or interstitial fluid flow conditions. The role of α3β1 in initial adhesion to laminin and collagen was assessed using adhesion assays and immunofluorescence.
resultsTumor onset in mice was independent of the presence of α3β1. In contrast, the depletion of α3β1 reduced the survival of mice and increased tumor growth and vascularization. Furthermore, Itga3 KO mice were significantly more likely to develop lung metastases and had an increased metastatic burden compared to WT mice. In vitro, the deletion of ITGA3 caused a significant increase in the cellular invasion of HER2-overexpressing SKBR3, AU565, and BT474 cells, but not of triple-negative MDA-MB-231. This invasion suppressing function of α3β1 in HER2-driven cells depended on the composition of the extracellular matrix and the interstitial fluid flow.
conclusionDownregulation of α3β1 in a HER2-driven mouse model and in HER2-overexpressing human mammary carcinoma cells promotes progression and invasiveness of tumors. The invasion-suppressive role of α3β1 was not observed in triple-negative mammary carcinoma cells, illustrating the tumor type-specific and complex function of α3β1 in breast cancer.
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