ArticleOncogene2022
Autocrine pro-legumain promotes breast cancer metastasis via binding to integrin αvβ3.
Article in Oncogene, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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
15 citing papers in PubMed, 19 citations in OpenAlex.
- Review
- Legumain Restrains Granuloma Formation by Inhibiting mTORC1/STAT1-Mediated M1 Macrophage Polarization in Sarcoidosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Monocyte-Derived LGMNResearch (Washington, D.C.) · 2026Article
- LGMN promotes crosstalk between macrophages and fibroblasts in pulmonary fibrosis: a potential therapeutic target.Frontiers in immunology · 2026Article
- A Tumor-homing nanoplatform for the co-delivery of triptolide and siRNA-A4B2 conspicuously overcomes peritoneum metastasis of ovarian cancer.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Integrin αvβ3 as a Non-Genomic Estrogen Receptor in Breast Cancer for Signaling Pathways and Crosstalk.Cells · 2025Review
- Application of Biomimetic SPIONs in Targeted Lung Cancer Therapy: Cell-Membrane Camouflage Technology and Lung Retention Enhancement Strategies.Pharmaceutics · 2025Review
- Membrane-wide screening identifies potential tissue-specific determinants of SARS-CoV-2 tropism.PLoS pathogens · 2025Article
- Oxidative Stress and Redox Signaling in Gastric Cancer: From Mechanisms to Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2025Review
- Cancer Cell Secreted Legumain Promotes Gastric Cancer Resistance to Anti-PD-1 Immunotherapy by Enhancing Macrophage M2 Polarization.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Hypoxia-driven protease legumain promotes immunosuppression in glioblastoma.Cell reports. Medicine · 2023Article
- Screening a DNA Aptamer Specifically Targeting Integrin β3 and Partially Inhibiting Tumor Cell Migration.Analytical chemistry · 2023Article
- Biomolecules Involved in Both Metastasis and Placenta Accreta Spectrum-Does the Common Pathophysiological Pathway Exist?Cancers · 2023Review
- Active targeting schemes for nano-drug delivery systems in osteosarcoma therapeutics.Journal of nanobiotechnology · 2023Review
- Clonorchis sinensis legumain promotes migration and invasion of cholangiocarcinoma cells via regulating tumor-related molecules.Parasites & vectors · 2023Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor metastasis is the leading cause of cancer-associated mortality. Unfortunately, the underlying mechanism of metastasis is poorly understood. Expression of legumain (LGMN), an endo-lysosomal cysteine protease, positively correlates with breast cancer metastatic progression and poor prognosis. Here, we report that LGMN is secreted in the zymogen form by motile breast cancer cells. Through binding to cell surface integrin αvβ3 via an RGD motif, the autocrine pro-LGMN activates FAK-Src-RhoA signaling in cancer cells and promotes cancer cell migration and invasion independent of LGMN protease activity. Either silencing LGMN expression or mutationally abolishing pro-LGMN‒αvβ3 interaction significantly inhibits cancer cell migration and invasion in vitro and breast cancer metastasis in vivo. Finally, we developed a monoclonal antibody against LGMN RGD motif, which blocks pro-LGMN‒αvβ3 binding, and effectively suppresses cancer cell migration and invasion in vitro and breast cancer metastasis in vivo. Thus, disruption of pro-LGMN‒integrin αvβ3 interaction may be a potentially promising strategy for treating breast cancer metastasis.
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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.