ArticleJournal of experimental & clinical cancer research : CR2019
GSK-3β regulates the endothelial-to-mesenchymal transition via reciprocal crosstalk between NSCLC cells and HUVECs in multicellular tumor spheroid models.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- What is the Impact of Endothelial-to-Mesenchymal Transition in Solid Tumours: A Qualitative Systematic Review and Quantitative Meta-Analysis.International journal of biological sciences · 2025Pooled it
- Gene expression and immune cell heterogeneity in inbred Amur tiger.BMC genomics · 2026Article
- 3D organotypic skin models recapitulate autoantibody-driven pemphigus pathomechanisms and targeted therapeutic response.Science advances · 2026Article
- Harnessing GSK-3β inhibition for lung cancer therapy: emerging opportunities and challenges.Medical oncology (Northwood, London, England) · 2025Review
- Review
- Loss of primary cilia promotes EphA2-mediated endothelial-to-mesenchymal transition in the ovarian tumor microenvironment.Molecular oncology · 2025Article
- Endothelial-Mesenchymal Transition in Tumor Microenvironment Promotes Neuroendocrine Differentiation of Prostate Cancer.Cancer science · 2025Article
- GSK-3 and BCL-XL inhibition mitigates the competitive advantage of APC-mutant colorectal cancer cells.Oncogenesis · 2025Article
- Shifting Shapes: The Endothelial-to-Mesenchymal Transition as a Driver for Cancer Progression.International journal of molecular sciences · 2025Review
- Inhibition of 11β-hydroxysteroid dehydrogenase 1 alleviates pulmonary fibrosis through inhibition of endothelial-to-mesenchymal transition and M2 macrophage polarization by upregulating heme oxygenase-1.Cell death & disease · 2025Article
- Secretomes From Non-Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial Endothelial-to-Mesenchymal Transition.Cancer medicine · 2025Article
- Endothelial remodeling in osteosarcomas: insights from patient samples and in vitro studies.American journal of cancer research · 2025Article
- Review
- Article
- Inhibition of DNMT3B expression in activated hepatic stellate cells overcomes chemoresistance in the tumor microenvironment of hepatocellular carcinoma.Scientific reports · 2024Article
- Characterization of gastric cancer-stimulated signaling pathways and function of CTGF in cancer-associated fibroblasts.Cell communication and signaling : CCS · 2024Article
- Endothelial-to-Mesenchymal Transition: Potential Target of Doxorubicin-Induced Cardiotoxicity.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2023Review
- Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models.BMB reports · 2023Review
- Article
- Optimization of tumor spheroid model in mesothelioma and lung cancers and anti-cancer drug testing in H2052/484 spheroids.Oncotarget · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundChemotherapy used for patients with unresectable lung tumors remains largely palliative due to chemoresistance, which may be due to tumor heterogeneity. Recently, multiple studies on the crosstalk between lung cancer cells and their tumor microenvironment (TME) have been conducted to understand and overcome chemoresistance in lung cancer.
methodsIn this study, we investigated the effect of reciprocal crosstalk between lung cancer cells and vascular endothelial cells using multicellular tumor spheroids (MCTSs) containing lung cancer cells and HUVECs.
resultsSecretomes from lung cancer spheroids significantly triggered the endothelial-to-mesenchymal transition (EndMT) process in HUVECs, compared to secretomes from monolayer-cultured lung cancer cells. Interestingly, expression of GSK-3β-targeted genes was altered in MCTSs and inhibition of this activity by a GSK-3β inhibitor induced reversion of EndMT in lung tumor microenvironments. Furthermore, we observed that HUVECs in MCTSs significantly increased the compactness of the spheroids and exhibited strong resistance against Gefitinib and Cisplatin, relative to fibroblasts, by facilitating the EndMT process in HUVECs. Subsequently, EndMT reversion contributed to control of chemoresistance, regardless of the levels of soluble transforming growth factor (TGF)-β. Using the MCTS xenograft mouse model, we demonstrated that inhibition of GSK-3β reduces lung cancer volume, and in combination with Gefitinib, has a synergistic effect on lung cancer therapy.
conclusionIn summary, these findings suggest that targeting EndMT through GSK-3β inhibition in HUVECs might represent a promising therapeutic strategy for lung cancer therapy.
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