ArticleOncotarget2015
Heregulin-HER3-HER2 signaling promotes matrix metalloproteinase-dependent blood-brain-barrier transendothelial migration of human breast cancer cell lines.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 72 citations in OpenAlex.
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- Association Between Human Epidermal Growth Factor Receptor 2-Low Status and Time to Development of Brain Metastases Among Patients With Breast Cancer: A Retrospective Cohort Study.JCO precision oncology · 2025Article
- Breaking boundaries: role of the brain barriers in metastatic process.Fluids and barriers of the CNS · 2025Review
- Breast Tumor Metastasis and Its Microenvironment: It Takes Both Seed and Soil to Grow a Tumor and Target It for Treatment.Cancers · 2024Review
- Navigating the Blood-Brain Barrier: Challenges and Therapeutic Strategies in Breast Cancer Brain Metastases.International journal of molecular sciences · 2023Review
- Breast cancer brain metastasis: from etiology to state-of-the-art modeling.Journal of biological engineering · 2023Review
- Leptomeningeal Metastasis: A Review of the Pathophysiology, Diagnostic Methodology, and Therapeutic Landscape.Current oncology (Toronto, Ont.) · 2023Review
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- Identification and validation of a novel stress granules-related prognostic model in colorectal cancer.Frontiers in genetics · 2023Article
- Breast cancer recurrence: factors impacting occurrence and survival.Irish journal of medical science · 2022Article
- Epigenome erosion and SOX10 drive neural crest phenotypic mimicry in triple-negative breast cancer.NPJ breast cancer · 2022Article
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- HER2-positive breast cancer brain metastasis: A new and exciting landscape.Cancer reports (Hoboken, N.J.) · 2022Review
- Evolving management of HER2+ breast cancer brain metastases and leptomeningeal disease.Journal of neuro-oncology · 2022Review
- Article
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
HER2-positive breast tumors are associated with a high risk of brain relapse. HER3 is thought to be an indispensible signaling substrate for HER2 (encoded by ERBB2) and is induced in breast cancer-brain metastases, though the molecular mechanisms by which this oncogenic dimer promotes the development of brain metastases are still elusive. We studied the effects of the HER3-HER2 ligand, heregulin (neuregulin-1, broadly expressed in the brain), on luminal breast cancer cell lines in vitro. Treatment of SKBr3 (ERBB2-amplified), MDA-MB-361 (ERBB2-amplified, metastatic brain tumor-derived) and MCF7 (HER2-positive, not ERBB2-amplified) cells with exogenous heregulin increased proliferation and adhesive potential, concomitant with induction of cyclin D1 and ICAM-1, and suppression of p27. All three cell lines invaded through matrigel toward a heregulin chemotactic signal in transwell experiments, associated with activation of extracellular cathepsin B and matrix metalloproteinase-9 (MMP-9). Moreover, heregulin induced breast cancer cell transmigration across a tight barrier of primary human brain microvascular endothelia. This was dependent on the activity of HER2, HER3 and MMPs, and was completely abrogated by combination HER2-HER3 blockade using Herceptin® and the humanized HER3 monoclonal antibody, EV20. Collectively these data suggest mechanisms by which the HER3-HER2 dimer promotes development of metastatic tumors in the heregulin-rich brain microenvironment.
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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.