EMB-driven glioblastoma multiforme progression via the MCT4/GPX3 axis: therapeutic inhibition by Ganxintriol A

Abstract Background Embigin (EMB) is a transmembrane glycoprotein highly expressed in glioblastoma multiforme (GBM), yet its role in GBM progression remains unclear. In this study, we investigate the function of intracellular EMB in promoting GBM progression and evaluate the effect of Ganxintriol A,...

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Main Authors: Bo Cheng, Jing Liu, Ling Gao, Ziwen Zhu, Yang Yang, Shangqi Liu, Xiaojin Wu
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Journal of Translational Medicine
Online Access:https://doi.org/10.1186/s12967-025-06290-z
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author Bo Cheng
Jing Liu
Ling Gao
Ziwen Zhu
Yang Yang
Shangqi Liu
Xiaojin Wu
author_facet Bo Cheng
Jing Liu
Ling Gao
Ziwen Zhu
Yang Yang
Shangqi Liu
Xiaojin Wu
author_sort Bo Cheng
collection DOAJ
description Abstract Background Embigin (EMB) is a transmembrane glycoprotein highly expressed in glioblastoma multiforme (GBM), yet its role in GBM progression remains unclear. In this study, we investigate the function of intracellular EMB in promoting GBM progression and evaluate the effect of Ganxintriol A, a traditional Chinese herbal extract, in GBM treatment. Methods Bioinformatics datasets were utilized to assess EMB expression and its prognostic value in GBM patients. In vitro experiments such as PCR、western blot,CCK8,transwell,wound healing,clone formation and flow cytometry assays were conducted to examine EMB’s biological functions and underlying mechanisms in GBM cell lines. Additionally, we constructed a subcutaneous tumor model in nude mice and evaluated the effect of traditional Chinese medicine extract Ganxintriol A on the progression of GBM through in vivo and in vitro experiments. Results EMB is highly expressed in GBM and is associated with poor prognosis in GBM patients. EMB overexpression accelerated GBM progression, whereas EMB knockdown had the opposite effect. Further analysis revealed that EMB upregulated epithelial-mesenchymal transition (EMT) and glycolysis while maintaining glutathione (GSH) redox balance by inducing monocarboxylate transporter 4 (MCT4) and glutathione peroxidase 3 (GPX3) expression. Treatment with Ganxintriol A significantly downregulated EMB expression, effectively inhibiting GBM progression both in vitro and in vivo. Conclusions This study highlights EMB as an independent prognostic biomarker for GBM and reveals a novel mechanism by which EMB drives GBM progression. Additionally, Ganxintriol A is identified as a promising therapeutic candidate for GBM treatment.
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spelling doaj-art-e466ed48e54f4e639352b3397d80c2da2025-08-20T01:57:25ZengBMCJournal of Translational Medicine1479-58762025-03-0123111410.1186/s12967-025-06290-zEMB-driven glioblastoma multiforme progression via the MCT4/GPX3 axis: therapeutic inhibition by Ganxintriol ABo Cheng0Jing Liu1Ling Gao2Ziwen Zhu3Yang Yang4Shangqi Liu5Xiaojin Wu6Department of Psychiatry, The Affiliated Xuzhou Eastern Hospital of Xuzhou Medical UniversityDepartment of Neurology, The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical UniversityDepartment of Pharmacy, The Affiliated Huaihai Hospital of Xuzhou Medical UniversityDepartment of Neurology, Tongji Hospital, School of Medicine, Tongji UniversityDepartment of Pharmacy, The Affiliated Huaihai Hospital of Xuzhou Medical UniversityDepartment of Neurology, Xuzhou Central Hospital, the Affiliated Xuzhou Clinical College of Xuzhou Medical UniversityDepartment of Radiation Oncology, Xuzhou Central Hospital, the Affiliated Xuzhou Clinical College of Xuzhou Medical UniversityAbstract Background Embigin (EMB) is a transmembrane glycoprotein highly expressed in glioblastoma multiforme (GBM), yet its role in GBM progression remains unclear. In this study, we investigate the function of intracellular EMB in promoting GBM progression and evaluate the effect of Ganxintriol A, a traditional Chinese herbal extract, in GBM treatment. Methods Bioinformatics datasets were utilized to assess EMB expression and its prognostic value in GBM patients. In vitro experiments such as PCR、western blot,CCK8,transwell,wound healing,clone formation and flow cytometry assays were conducted to examine EMB’s biological functions and underlying mechanisms in GBM cell lines. Additionally, we constructed a subcutaneous tumor model in nude mice and evaluated the effect of traditional Chinese medicine extract Ganxintriol A on the progression of GBM through in vivo and in vitro experiments. Results EMB is highly expressed in GBM and is associated with poor prognosis in GBM patients. EMB overexpression accelerated GBM progression, whereas EMB knockdown had the opposite effect. Further analysis revealed that EMB upregulated epithelial-mesenchymal transition (EMT) and glycolysis while maintaining glutathione (GSH) redox balance by inducing monocarboxylate transporter 4 (MCT4) and glutathione peroxidase 3 (GPX3) expression. Treatment with Ganxintriol A significantly downregulated EMB expression, effectively inhibiting GBM progression both in vitro and in vivo. Conclusions This study highlights EMB as an independent prognostic biomarker for GBM and reveals a novel mechanism by which EMB drives GBM progression. Additionally, Ganxintriol A is identified as a promising therapeutic candidate for GBM treatment.https://doi.org/10.1186/s12967-025-06290-z
spellingShingle Bo Cheng
Jing Liu
Ling Gao
Ziwen Zhu
Yang Yang
Shangqi Liu
Xiaojin Wu
EMB-driven glioblastoma multiforme progression via the MCT4/GPX3 axis: therapeutic inhibition by Ganxintriol A
Journal of Translational Medicine
title EMB-driven glioblastoma multiforme progression via the MCT4/GPX3 axis: therapeutic inhibition by Ganxintriol A
title_full EMB-driven glioblastoma multiforme progression via the MCT4/GPX3 axis: therapeutic inhibition by Ganxintriol A
title_fullStr EMB-driven glioblastoma multiforme progression via the MCT4/GPX3 axis: therapeutic inhibition by Ganxintriol A
title_full_unstemmed EMB-driven glioblastoma multiforme progression via the MCT4/GPX3 axis: therapeutic inhibition by Ganxintriol A
title_short EMB-driven glioblastoma multiforme progression via the MCT4/GPX3 axis: therapeutic inhibition by Ganxintriol A
title_sort emb driven glioblastoma multiforme progression via the mct4 gpx3 axis therapeutic inhibition by ganxintriol a
url https://doi.org/10.1186/s12967-025-06290-z
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