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Updated: May 20, 2026
The Clinical Application of Tumor Treating Fields Therapy in Glioblastoma
Published on: April 16, 2019
Tumor Electric Field Therapy Inhibits Epithelial-Mesenchymal Transition, Invasion, and Migration of Glioblastoma by
Cheng Sun1,2,3, Yuyang Liu1,4,5, Junyi Chen6
1Medical School of, Chinese PLA, Beijing, China.
Background:
Glioblastoma (GBM) is among the most aggressive and treatment-resistant primary brain tumors. The mesenchymal subtype of GBM shows a particularly unfavorable prognosis. Epithelial-mesenchymal transition (EMT) is a critical phenotypic characteristic of this subtype. Tumor electric field therapy (TEFT) has emerged as a promising adjuvant therapy, but its underlying anti-GBM mechanisms remain incompletely elucidated.
Methods:
Key molecular targets of TEFT were identified through integrated multi-omics data analysis. U87, U251, and T98G cell lines received TEFT treatment at 200 kHz and 2.2 V/cm for 72 h. Stable cell models with CXCL14 and c-FOS knockdown or overexpression were established using lentiviral vectors. Cellular phenotypes were assessed via wound healing assays, transwell migration and invasion assays, and western blot analysis. The regulatory hierarchy between c-FOS and CXCL14 was verified via chromatin immunoprecipitation (ChIP) assays and rescue experiments. Mechanistic insights were validated in orthotopic nude mouse models and clinical patient specimens.
Results:
CXCL14 was identified by integrated bioinformatics analysis. It showed significant overexpression in mesenchymal subtypes and was strongly associated with poor prognosis. Single-cell sequencing analysis suggested a significant increase in the EMT score of the subgroup with high CXCL14 expression. TEFT induced a morphological shift from mesenchymal to epithelial-like characteristics. It downregulated mesenchymal markers, including N-cadherin, Vimentin, and Snail, while upregulating E-cadherin. Mechanistic investigations demonstrated that TEFT promoted the degradation of c-FOS, leading to CXCL14 downregulation and subsequent inhibition of EMT. In vivo experiments confirmed the critical role of the c-FOS/CXCL14 axis in regulating GBM invasion and migration potential.
Conclusion:
This study first revealed a novel mechanism which TEFT suppressed EMT in GBM via the c-FOS/CXCL14 axis. These findings provided a new therapeutic target and a theoretical foundation for optimizing TEFT efficacy.
Insights
Tumor electric field therapy (TEFT) suppresses glioblastoma (GBM) by targeting the c-FOS/CXCL14 axis, inhibiting epithelial-mesenchymal transition (EMT). This reveals a new mechanism and therapeutic target for aggressive GBM subtypes.
Area of Science:
- Oncology
- Molecular Biology
- Biophysics
Background:
- Glioblastoma (GBM) is an aggressive brain tumor, with the mesenchymal subtype exhibiting poor prognosis due to epithelial-mesenchymal transition (EMT).
- Tumor electric field therapy (TEFT) shows promise as an adjuvant treatment, but its anti-GBM mechanisms require further elucidation.
Purpose of the Study:
- To identify molecular targets of TEFT in GBM.
- To elucidate the mechanism by which TEFT suppresses GBM growth and invasion.
- To validate the role of the c-FOS/CXCL14 axis in TEFT's efficacy.
Main Methods:
- Integrated multi-omics analysis to identify key molecular targets.
- In vitro studies using GBM cell lines (U87, U251, T98G) treated with TEFT.
- Establishment of stable cell models with altered CXCL14 and c-FOS expression.
- In vivo validation in orthotopic nude mouse models and analysis of clinical patient specimens.
Main Results:
- CXCL14 was identified as significantly overexpressed in mesenchymal GBM and associated with poor prognosis.
- TEFT treatment induced a shift from mesenchymal to epithelial-like characteristics, downregulating mesenchymal markers and upregulating E-cadherin.
- TEFT promoted c-FOS degradation, leading to CXCL14 downregulation and subsequent inhibition of EMT.
- The c-FOS/CXCL14 axis was confirmed to regulate GBM invasion and migration in vivo.
Conclusions:
- This study reveals a novel mechanism of TEFT in suppressing GBM EMT via the c-FOS/CXCL14 axis.
- The c-FOS/CXCL14 axis represents a potential therapeutic target for optimizing TEFT efficacy in GBM treatment.
