ArticleJournal of experimental & clinical cancer research : CR2022
ARHGEF37 overexpression promotes extravasation and metastasis of hepatocellular carcinoma via directly activating Cdc42.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
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- Tumor-Associated Pericytes: Tumorigenicity and Targeting for Cancer Therapy.Current vascular pharmacology · 2026Review
- Hypoxia drives cervical cancer progression via OCT4/ORAI3-dependent glycolysis and CaCellular and molecular life sciences : CMLS · 2025Article
- Novel Evolutionarily Conserved Oncogene COA4 is Driven by KRAS Mutant and Promotes Cancer Metastasis Through Dual Mitochondrial Metabolism-Dependent and -Independent Mechanisms.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Pericytes in hematogenous metastasis: mechanistic insights and therapeutic approaches.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Epithelial-to-mesenchymal transition (EMT) and cancer metastasis: the status quo of methods and experimental models 2025.Molecular cancer · 2025Review
- [RGL1 overexpression promotes metastasis of colorectal cancer by upregulating motile focal adhesion assemblyNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Invadopodia in cancer metastasis: dynamics, regulation, and targeted therapies.Journal of translational medicine · 2025Review
- Serum CDC42 level change during abiraterone plus prednisone treatment and its association with prognosis in metastatic castration-resistant prostate cancer patients.Discover oncology · 2025Article
- Multi-disease transcriptomic analysis of sex hormone genes reveals a novel prognostic model for thyroid cancer with breast cancer correlations.Frontiers in oncology · 2025Article
- NUCKS1 exacerbates hepatocellular carcinoma cell proliferation and metastasis via the upregulation of Cdc42.American journal of cancer research · 2025Article
- Identification of diagnostic biomarkers for fibromyalgia using gene expression analysis and machine learning.Frontiers in genetics · 2025Article
- Construction of a stromal cell-related prognostic signature based on a 101-combination machine learning framework for predicting prognosis and immunotherapy response in triple-negative breast cancer.Frontiers in immunology · 2025Article
- Mitogen-activated protein kinase pathway and four genes involved in the development of benign prostatic hyperplasia:Frontiers in immunology · 2025Article
- Single cell landscape of potential mechanisms in primary and metastatic hepatocellular carcinoma.Scientific reports · 2024Article
- Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives.Signal transduction and targeted therapy · 2024Review
- Article
- DAB2IP suppresses invadopodia formation through destabilizing ALK by interacting with USP10 in breast cancer.iScience · 2023Article
- ASAP2 interrupts c-MET-CIN85 interaction to sustain HGF/c-MET-induced malignant potentials in hepatocellular carcinoma.Experimental hematology & oncology · 2023Article
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe extravasation capability of hepatocellular carcinoma (HCC) cells plays a vital role in distant metastasis. However, the underlying mechanism of extravasation in HCC lung metastasis remains largely unclear.
methodsThe expression of ARHGEF37 in human HCC specimens and HCC cell lines was examined by quantitative RT-PCR, western blot, and immunohistochemistry (IHC) analyses. The biological roles and mechanisms of ARHGEF37/Cdc42 in promoting lung metastasis were investigated in vitro and in vivo using cell lines, patient samples, xenograft models.
resultsIn the current study, we found that Rho guanine nucleotide exchange factor 37 (ARHGEF37) was upregulated in human HCC samples and was associated with tumor invasiveness, pulmonary metastasis and poor prognosis. Overexpressing ARHGEF37 significantly enhanced the extravasation and metastatic capability of HCC cells via facilitating tumor cell adhesion to endothelial cells and trans-endothelial migration. Mechanistically, ARHGEF37 directly interacted with and activated Cdc42 to promote the invadopodia formation in HCC cells, which consequently disrupted the interaction between endothelial cells and pericytes. Importantly, treatment with ZCL278, a specific inhibitor of Cdc42, dramatically inhibited the attachment of ARHGEF37-overexpressing HCC cells to endothelial cells, and the adherence and extravasation in the lung alveoli, resulting in suppression of lung metastasis in mice.
conclusionOur findings provide a new insight into the underlying mechanisms on the ARHGEF37 overexpression-mediated extravasation and pulmonary metastasis of HCC cells, and provided a potential therapeutic target for the prevention and treatment of HCC pulmonary metastasis.
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