ArticleJournal of cellular biochemistry2010
Modulation of GEF-H1 induced signaling by heparanase in brain metastatic melanoma cells.
Article in Journal of cellular biochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Clinical outcome and molecular characterization of brain metastases from esophageal and gastric cancer: a systematic review.Medical oncology (Northwood, London, England) · 2017Pooled it
- Mechanistic and preclinical evaluation of SIRT3 as a therapeutic target in melanoma.Journal of dermato-oncology · 2026Article
- Androgen deprivation restores ARHGEF2 to promote neuroendocrine differentiation of prostate cancer.Cell death & disease · 2022Article
- Correlation Imputation for Single-Cell RNA-seq.Journal of computational biology : a journal of computational molecular cell biology · 2022Article
- High ARHGEF2 (GEF-H1) Expression is Associated with Poor Prognosis Via Cell Cycle Regulation in Patients with Pancreatic Cancer.Annals of surgical oncology · 2021Article
- Rho GTPases in the Amygdala-A Switch for Fears?Cells · 2020Review
- Perlecan domain I gradients establish stable biomimetic heparin binding growth factor gradients for cell migration in hydrogels.Acta biomaterialia · 2019Article
- Extracellular histones are the ligands for the uptake of exosomes and hydroxyapatite-nanoparticles by tumor cells via syndecan-4.FEBS letters · 2018Article
- Evaluation of the C-domain of heparanase during AGE-induced macrophage inflammatory response.Experimental and therapeutic medicine · 2017Article
- Exosomes from metastatic cancer cells transfer amoeboid phenotype to non-metastatic cells and increase endothelial permeability: their emerging role in tumor heterogeneity.Scientific reports · 2017Article
- Embracing rejection: Immunologic trends in brain metastasis.Oncoimmunology · 2016Review
- Guanine nucleotide exchange factor H1 can be a new biomarker of melanoma.Biologics : targets & therapy · 2016Article
- Melanoma brain metastases: an unmet challenge in the era of active therapy.Current oncology reports · 2013Review
- Role of the blood-brain barrier in the formation of brain metastases.International journal of molecular sciences · 2013Review
- Brain metastases from colorectal cancer: microenvironment and molecular mechanisms.International journal of molecular sciences · 2012Review
- Heparanase-induced GEF-H1 signaling regulates the cytoskeletal dynamics of brain metastatic breast cancer cells.Molecular cancer research : MCR · 2012Article
- Antithetic roles of proteoglycans in cancer.Cellular and molecular life sciences : CMLS · 2012Review
- Stimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion.PloS one · 2012Article
- Heparanase Modulates Shh and Wnt3a Signaling in Human Medulloblastoma Cells.Experimental and therapeutic medicine · 2011Article
- Decoding melanoma metastasis.Cancers · 2010Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mechanisms of brain metastatic melanoma (BMM) remain largely unknown. Understanding the modulation of signaling pathways that alter BMM cell invasion and metastasis is critical to develop new therapies for BMM. Heparanase has been widely implicated in cancer and is the dominant mammalian endoglycosidase which degrades heparan sulfate chains of proteoglycans (HSPG) including syndecans (SDCs). Recent findings also indicate that heparanase possesses non-enzymatic functions in its latent form. We hypothesized that extracellular heparanase modulates BMM cell signaling by involving SDC1/4 carboxy terminal-associated proteins and downstream targets. We digested BMM cell surface HS with human recombinant active or latent heparanase to delineate their effects on cytoskeletal dynamics and cell invasiveness. We identified the small GTPase guanine nucleotide exchange factor-H1 (GEF-H1) as a new component of a SDC signaling complex that is differentially expressed in BMM cells compared to corresponding non-metastatic counterparts. Second, knockdown of GEF-H1, SDC1, or SDC4 decreased BMM cell invasiveness and GEF-H1 modulated small GTPase activity of Rac1 and RhoA in conjunction with heparanase treatment. Third, both active and latent forms of heparanase affected Rac1 and RhoA activity; notably increasing RhoA activity. Both forms of heparanase were found to mediate the expression and subcellular localization of GEF-H1, and treatment of BMM with latent heparanase modulated SDC1/4 gene expression. Finally, treatment with exogenous heparanase downregulated BMM cell invasion. These studies indicate the relevance of heparanase signaling pathways in BMM progression, and provide insights into the molecular mechanisms regulating HSPG signaling in response to exogenous heparanase.
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