ArticlePloS one2013
Lactate-modulated induction of THBS-1 activates transforming growth factor (TGF)-beta2 and migration of glioma cells in vitro.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 56 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
56 citing papers in PubMed, 90 citations in OpenAlex.
- IGFBP7 and CCT2 are novel lactylation-driven mediators of endothelial-to-mesenchymal transition in idiopathic pulmonary fibrosis.Functional & integrative genomics · 2025Article
- Cell Settling, Migration, and Stochastic Cancer Gene Expression Suggest Potassium Membrane Flux May Initiate pH Reversal.Biomolecules · 2025Article
- A review of the link between the lactate-GPR81 axis and mitochondrial angiopathy in MELAS based on imaging characteristics.Journal of neurology · 2025Review
- Lactate dehydrogenase A: a potential new target for tumor drug resistance intervention.Journal of translational medicine · 2025Review
- TGFβ2 Promotes the Construction of Fibrotic and Immunosuppressive Tumor Microenvironment in Pancreatic Adenocarcinoma: A Comprehensive Analysis.Molecular biotechnology · 2025Article
- Transcriptome signatures of human neural stem cells derived from LRRK2 gene therapeutic cells.Scientific reports · 2025Article
- Bulk and single-cell transcriptome revealed the metabolic heterogeneity in human glioma.Heliyon · 2025Article
- Blastocyst-Derived Lactate as a Key Facilitator of Implantation.Biomolecules · 2025Review
- Targeting Wnt-driven metabolic adaptations in cancer: integrating glycolysis, glutaminolysis, IDO1-mediated immune evasion, and therapeutic delivery strategies.Frontiers in cell and developmental biology · 2025Review
- Cross-talk between disulfidptosis and immune check point genes defines the tumor microenvironment for the prediction of prognosis and immunotherapies in glioblastoma.Scientific reports · 2024Article
- SLC2A3 promotes tumor progression through lactic acid-promoted TGF-β signaling pathway in oral squamous cell carcinoma.PloS one · 2024Article
- Review
- Lactic acidosis induces metabolic and phenotypic reprogramming in cholangiocarcinoma cells via the upregulation of thrombospondin-1.Cancer science · 2023Article
- Small Molecules Targeting the RNA-Binding Protein HuR Inhibit Tumor Growth in Xenografts.Journal of medicinal chemistry · 2023Article
- Lactate dehydrogenases promote glioblastoma growth and invasion via a metabolic symbiosis.EMBO molecular medicine · 2022Article
- circRNA PLOD2 promotes tumorigenesis and Warburg effect in colon cancer by the miR-513a-5p/SIX1/LDHA axis.Cell cycle (Georgetown, Tex.) · 2022Article
- Classical epithelial-mesenchymal transition (EMT) and alternative cell death process-driven blebbishield metastatic-witch (BMW) pathways to cancer metastasis.Signal transduction and targeted therapy · 2022Review
- LINC01128 facilitates the progression of pancreatic cancer through up-regulation of LDHA by targeting miR-561-5p.Cancer cell international · 2022Article
- Molecular Mechanisms and Clinical Challenges of Glioma Invasion.Brain sciences · 2022Review
- Glycolysis, monocarboxylate transport, and purinergic signaling are key events inFrontiers in immunology · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAn important phenomenon observed in glioma metabolism is increased aerobic glycolysis in tumor cells, which is generally referred to as the Warburg effect. Transforming growth factor (TGF)-beta2, which we previously showed to be induced by lactic acid, is a key pathophysiological factor in glioblastoma, leading to increased invasion and severe local immunosuppression after proteolytic cleavage from its latency associated peptide. In this study we tested the hypothesis, that lactate regulates TGF-beta2 expression and glioma cell migration via induction of Thrombospondin-1 (THBS-1), a TGF-beta activating protein.
methodsLactate levels were reduced by knockdown of LDH-A using specific small interfering RNA (siRNA) and competitive inhibition of LDH-A by sodium oxamate. Knockdown of THBS-1 was performed using specific siRNA. Western Blot, qRT-PCR, and ELISA were used to investigate expression levels of LDH-A, LDH-B, TGF-beta2 and THBS-1. Migration of cells was examined by Spheroid, Scratch and Boyden Chamber assays.
resultsKnockdown of LDH-A with subsequent decrease of lactate concentration leads to reduced levels of THBS-1 and TGF-beta2 in glioma cells. Lactate addition increases THBS-1 protein, leading to increased activation of TGF-beta2. Inhibition of THBS-1 reduces TGF-beta2 protein and migration of glioma cells. Addition of synthetic THBS-1 can rescue reduced TGF-beta2 protein levels and glioma cell migration in siLDH-A treated cells.
conclusionWe define a regulatory cascade between lactate, THBS-1 and TGF-beta2, leading to enhanced migration of glioma cells. Our results demonstrate a specific interaction between tumor metabolism and migration and provide a better understanding of the mechanisms underlying glioma cell invasion.
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.