ArticleAnnals of biomedical engineering2011
Integrin β4 signaling promotes mammary tumor cell adhesion to brain microvascular endothelium by inducing ErbB2-mediated secretion of VEGF.
Article in Annals of biomedical engineering, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
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- Computational analysis of cancer cell adhesion in curved vessels affected by wall shear stress for prediction of metastatic spreading.Frontiers in bioengineering and biotechnology · 2024Article
- Mechanisms of Organ-Specific Metastasis of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2023Review
- Targeting of endothelial cells in brain tumours.Clinical and translational medicine · 2023Review
- The origin of brain malignancies at the blood-brain barrier.Cellular and molecular life sciences : CMLS · 2023Review
- The Brain Pre-Metastatic Niche: Biological and Technical Advancements.International journal of molecular sciences · 2023Review
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- Biology of breast cancer brain metastases and novel therapies targeting the blood brain barrier: an updated review.Medical oncology (Northwood, London, England) · 2023Review
- Integrins and the Metastasis-like Dissemination of Acute Lymphoblastic Leukemia to the Central Nervous System.Cancers · 2023Review
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- Genomics of Breast Cancer Brain Metastases: A Meta-Analysis and Therapeutic Implications.Cancers · 2023Article
- Integrin αvβ3 Is a Master Regulator of Resistance to TKI-Induced Ferroptosis in HER2-Positive Breast Cancer.Cancers · 2023Article
- Review
- Interacting with tumor cells weakens the intrinsic clockwise chirality of endothelial cells.APL bioengineering · 2022Article
- Leptomeningeal metastases in patients with human epidermal growth factor receptor 2 positive breast cancer: Real-world data from a multicentric European cohort.International journal of cancer · 2022Article
- KRAS Mutants Upregulate Integrin β4 to Promote Invasion and Metastasis in Colorectal Cancer.Molecular cancer research : MCR · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Prior studies have indicated that the β4 integrin promotes mammary tumor invasion and metastasis by combining with ErbB2 and amplifying its signaling capacity. However, the effector pathways and cellular functions by which the β4 integrin exerts these effects are incompletely understood. To examine if β4 signaling plays a role during mammary tumor cell adhesion to microvascular endothelium, we have examined ErbB2-transformed mammary tumor cells expressing either a wild-type (WT) or a signaling-defective form of β4 (1355T). We report that WT cells adhere to brain microvascular endothelium in vitro to a significantly larger extent as compared to 1355T cells. Interestingly, integrin β4 signaling does not exert a direct effect on adhesion to the endothelium or the underlying basement membrane. Rather, it enhances ErbB2-dependent expression of VEGF by tumor cells. VEGF in turn disrupts the tight and adherens junctions of endothelial monolayers, enabling the exposure of underlying basement membrane and increasing the adhesion of tumor cells to the intercellular junctions of endothelium. Inhibition of ErbB2 on tumor cells or the VEGFR-2 on endothelial cells suppresses mammary tumor cell adhesion to microvascular endothelium. Our results indicate that β4 signaling regulates VEGF expression by the mammary tumor cells thereby enhancing their adhesion to microvascular endothelium.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.