ArticleOncotarget2017
The matricellular protein CYR61 promotes breast cancer lung metastasis by facilitating tumor cell extravasation and suppressing anoikis.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Prognostic role of EGR1 in breast cancer: a systematic review.BMB reports · 2021Pooled it
- The TAZ-CAMTA1 Fusion Protein Promotes Tumorigenesis via Connective Tissue Growth Factor and Ras-MAPK Signaling in Epithelioid Hemangioendothelioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Blood-based detection of lung cancer using cysteine-rich angiogenic inducer 61 (CYR61) as a circulating protein biomarker: a pilot study.Molecular oncology · 2021Trial
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- The polarity protein Par3 enhances renal cell carcinoma metastasisCancer biology & medicine · 2025Article
- Metabolic reprogramming and signaling adaptations in anoikis resistance: mechanisms and therapeutic targets.Molecular and cellular biochemistry · 2025Review
- Review
- ERK3/MAPK6 promotes triple-negative breast cancer progression through collective migration and EMT plasticity.Frontiers in oncology · 2025Article
- Single-cell multi-modal chromatin profiles revealing epigenetic regulations of cells in hepatocellular carcinoma.Clinical and translational medicine · 2024Article
- Role of adhesion molecules in cancer and targeted therapy.Science China. Life sciences · 2024Review
- Novel Anti-Cancer Products Targeting AMPK: Natural Herbal Medicine against Breast Cancer.Molecules (Basel, Switzerland) · 2023Review
- Senescence of Tumor Cells in Anticancer Therapy-Beneficial and Detrimental Effects.International journal of molecular sciences · 2022Review
- Article
- Mechanisms of Cell Adhesion Molecules in Endocrine-Related Cancers: A Concise Outlook.Frontiers in endocrinology · 2022Review
- Depletion of CCN1/CYR61 reduces triple-negative/basal-like breast cancer aggressiveness.American journal of cancer research · 2022Article
- The CCN axis in cancer development and progression.Journal of cell communication and signaling · 2021Review
- Bothrops Jararaca Snake Venom Modulates Key Cancer-Related Proteins in Breast Tumor Cell Lines.Toxins · 2021Article
- Nonsense-mediated RNA decay and its bipolar function in cancer.Molecular cancer · 2021Review
- Hippo/TEAD4 signaling pathway as a potential target for the treatment of breast cancer.Oncology letters · 2021Review
- Hypoxia-induced alternative splicing in human diseases: the pledge, the turn, and the prestige.Cellular and molecular life sciences : CMLS · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Matricellular proteins play multiple roles in primary tumor growth, local invasion and tumor angiogenesis. However, their contribution to metastasis and the putative mechanisms involved are less well characterized. In ER-negative human breast cancer, elevated expression levels of the matricellular protein Cysteine-rich angiogenic inducer 61 (CYR61) are associated with more aggressive progression. Here, we investigated the role of CYR61 in breast cancer lung metastasis using the triple negative human breast cancer cell lines MDA-MB-231 and SUM159. Silencing of CYR61 significantly decreased lung metastasis from tumors orthotopically implanted in pre-irradiated or naive mammary tissue and upon tail vein injection. Constitutive CYR61 silencing impaired cancer cell extravasation to the lung during the first 24 hours after tail vein injection. In contrast, CYR61 inducible silencing starting 24 hours after cancer cell injection had no impact on lung metastasis formation. In vitro experiments revealed that CYR61 silencing decreased cancer cell transendothelial migration and motility, reduced CYR61 levels present at the cell surface and sensitized cancer cells to anoikis. Furthermore, we demonstrate that CYR61-dependent cell survival under non-adhesive conditions relied, at least partially, on β1 integrin ligation and AMPKα signaling while it was independent of AKT, FAK and ERK1/2 activation. Our data provide the first evidence that CYR61 promotes breast cancer lung metastasis by facilitating tumor cell extravasation and protecting from anoikis during initial seeding to the lung. The uncovered CYR61-β1 integrin-AMPKα axis may serve as a potential therapeutic target to prevent breast cancer metastasis to the lung.
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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.