ArticleCell death & disease2018
AMPK-dependent autophagy upregulation serves as a survival mechanism in response to Tumor Treating Fields (TTFields).
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
78 citing papers in PubMed, 106 citations in OpenAlex.
- Exploratory analysis of miRNAs-21, -26a, -34a, -181c, -181d, and -485-5p as potential biomarkers for tumor treating fields sensitivity in primary glioblastoma cell cultures.Brain tumor pathology · 2026Article
- Tumor Treating Fields and the Glioblastoma Microenvironment: Mechanistic Convergences with Radiotherapy.Cancers · 2026Review
- Efficacy and immunogenic effects of Tumor Treating Fields (TTFields) in preclinical models of pancreatic ductal adenocarcinoma, with and without gemcitabine/nab-paclitaxel.International journal of cancer · 2026Article
- Microbiome Integrity Protects Against Glial-Mediated Tau and Amyloid Pathology Through Circadian and Autophagy Homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Effects of Multifrequency Electromagnetic Pulses on tumor growth in immunocompetent mice.Scientific reports · 2026Article
- Safety and Efficacy of Tumor-Treating Fields (TTFields) Therapy for Pediatric High-Grade Glioma: Results of a Prespecified Interim Analysis of the First Three Cases.Children (Basel, Switzerland) · 2026Article
- Development and Preliminary Validation of a Wearable Tumor Treating Fields Device for Breast Cancer Therapy.Breast cancer (Dove Medical Press) · 2026Article
- Tumor treating fields in malignant pleural mesothelioma: from cytoskeletal collapse to immunophenotypic conversion.Frontiers in immunology · 2026Review
- Selective antitumor activity of Tumor Treating Fields (TTFields) involving molecular factors in cancer cells and tumor microenvironment.Translational oncology · 2025Review
- Novel combination therapy with phenformin enhances the effects of lenvatinib in hepatocellular carcinoma via AMPK-mediated PDGFRβ degradation.Cancer cell international · 2025Article
- The therapeutic efficacy and application prospects of tumor-treating fields (TTFields) in resolving malignant tumors of central nervous system.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- The Evidence That Brain Cancers Could Be Effectively Treated with In-Home Radiofrequency Waves.Cancers · 2025Article
- The transcriptomic fingerprint of cancer response to Tumor Treating Fields (TTFields).Cell death discovery · 2025Article
- Advancement in tumor treating fields of mechanism, clinical applications, and future directions.Discover oncology · 2025Review
- Tumor-Treating Fields Alter Nanomechanical Properties of Pancreatic Ductal Adenocarcinoma Cells Co-Cultured with Extracellular Matrix.Journal of functional biomaterials · 2025Article
- Tumor Treating Fields (TTFields) Therapy in Unresectable Pleural Mesothelioma: Overview of Efficacy, Safety, and Future Outlook.Current treatment options in oncology · 2025Review
- Role of the PI3K/AKT signaling pathway in the cellular response to Tumor Treating Fields (TTFields).Cell death & disease · 2025Article
- Recent advances in Tumor Treating Fields (TTFields) therapy for glioblastoma.The oncologist · 2025Review
- Tumor-treating fields in cancer therapy: advances of cellular and molecular mechanisms.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Hydrogel and scalp/skin conductivities impact dose from tumor treating fields.Frontiers in bioengineering and biotechnology · 2025Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor Treating Fields (TTFields), an approved treatment modality for glioblastoma, are delivered via non-invasive application of low-intensity, intermediate-frequency, alternating electric fields. TTFields application leads to abnormal mitosis, aneuploidy, and increased cell granularity, which are often associated with enhancement of autophagy. In this work, we evaluated whether TTFields effected the regulation of autophagy in glioma cells. We found that autophagy is upregulated in glioma cells treated with TTFields as demonstrated by immunoblot analysis of the lipidated microtubule-associated protein light chain 3 (LC3-II). Fluorescence and transmission electron microscopy demonstrated the presence of LC3 puncta and typical autophagosome-like structures in TTFields-treated cells. Utilizing time-lapse microscopy, we found that the significant increase in the formation of LC3 puncta was specific to cells that divided during TTFields application. Evaluation of selected cell stress parameters revealed an increase in the expression of the endoplasmic reticulum (ER) stress marker GRP78 and decreased intracellular ATP levels, both of which are indicative of increased proteotoxic stress. Pathway analysis demonstrated that TTFields-induced upregulation of autophagy is dependent on AMP-activated protein kinase (AMPK) activation. Depletion of AMPK or autophagy-related protein 7 (ATG7) inhibited the upregulation of autophagy in response to TTFields, as well as sensitized cells to the treatment, suggesting that cancer cells utilize autophagy as a resistance mechanism to TTFields. Combining TTFields with the autophagy inhibitor chloroquine (CQ) resulted in a significant dose-dependent reduction in cell growth compared with either TTFields or CQ alone. These results suggest that dividing cells upregulate autophagy in response to aneuploidy and ER stress induced by TTFields, and that AMPK serves as a key regulator of this process.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.