ArticleMolecular cancer research : MCR2010
Epidermal growth factor-induced heparanase nucleolar localization augments DNA topoisomerase I activity in brain metastatic breast cancer.
Article in Molecular cancer research : MCR, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 54 citations in OpenAlex.
- Heparan Sulfate Proteoglycans (HSPGs) and Their Degradation in Health and Disease.Biomolecules · 2025Review
- The origin of brain malignancies at the blood-brain barrier.Cellular and molecular life sciences : CMLS · 2023Review
- Review
- Molecular landscape and emerging therapeutic strategies in breast cancer brain metastasis.Therapeutic advances in medical oncology · 2023Review
- Thermal stabilization of diverse biologics using reversible hydrogels.Science advances · 2022Article
- HER2-positive breast cancer brain metastasis: A new and exciting landscape.Cancer reports (Hoboken, N.J.) · 2022Review
- Molecular Mechanisms Associated with Brain Metastases in HER2-Positive and Triple Negative Breast Cancers.Cancers · 2021Review
- Biology of the Heparanase-Heparan Sulfate Axis and Its Role in Disease Pathogenesis.Seminars in thrombosis and hemostasis · 2021Review
- Heparanase, cell signaling, and viral infections.Cellular and molecular life sciences : CMLS · 2020Review
- Heparanase and the hallmarks of cancer.Journal of translational medicine · 2020Review
- Heparanase from triple‑negative breast cancer and platelets acts as an enhancer of metastasis.International journal of oncology · 2020Article
- Heparanase: A Dynamic Promoter of Myeloma Progression.Advances in experimental medicine and biology · 2020Review
- Foe or friend? Janus-faces of the neurovascular unit in the formation of brain metastases.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Review
- Mechanisms of heparanase inhibitors in cancer therapy.Experimental hematology · 2016Review
- Human telomerase reverse transcriptase (hTERT) promotes gastric cancer invasion through cooperating with c-Myc to upregulate heparanase expression.Oncotarget · 2016Article
- EGFR and HER2 signaling in breast cancer brain metastasis.Frontiers in bioscience (Elite edition) · 2016Article
- Notes for developing a molecular test for the full characterization of circulating tumor cells.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2015Review
- Heparanase promotes tumor infiltration and antitumor activity of CAR-redirected T lymphocytes.Nature medicine · 2015Article
- Heparanase mediates a novel mechanism in lapatinib-resistant brain metastatic breast cancer.Neoplasia (New York, N.Y.) · 2015Article
- Cell-autonomous heparanase modulates self-renewal and migration in bone marrow-derived mesenchymal stem cells.Journal of biomedical science · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Identification of molecular mechanisms responsible for brain metastatic breast cancer (BMBC) is imperative to develop novel therapies. However, current understanding of the molecular circuitry that governs BMBC dissemination remains fragmentary. Heparanase (HPSE) is the only functional mammalian endoglycosidase whose activity correlates with cancer metastasis, angiogenesis, and the reduced postoperative survival of cancer patients, making it an active target for anticancer therapeutics. We hypothesized that human epidermal growth factor receptor 2 (HER2)/epidermal growth factor receptor (EGFR) activation promotes HPSE function in human BMBC. To address this, we examined HPSE content, activity, and intracellular trafficking in a HER2/EGFR-expressing BMBC model system and show that HPSE is present, functional, and correlates with HER2 status. Further, we showed that EGF induced nucleolar translocation of HPSE in these cells in a dose- and time-dependent manner upon activation of HER2/EGFR. Knockdowns of HER2/EGFR by small interference RNA abolished EGF-induced HPSE nucleolar translocalization. It was also noted that nucleolar HPSE modulates DNA topoisomerase I (Topo I), an enzyme that is highly present in nucleoli, essential for DNA replication and transcription in a variety of tumors, and inhibited by heparan sulfate. Evidence is provided that HPSE can regulate Topo I activity, which subsequently affects BMBC cell proliferation. Finally, we showed that the nucleolar presence of HPSE with Topo I colocalization is detected only in HER2-overexpressing BMBC patient specimens. Altogether, these findings support the notion that HPSE is a critical downstream target of HER2 mechanisms driving BMBC and is potentially relevant for BMBC therapeutic interventions.
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