ArticlePloS one2011
Acidic environment leads to ROS-induced MAPK signaling in cancer cells.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 155 citations in OpenAlex.
- Review
- TMEM16E-mediated macropinocytosis promotes cell survival under acidic stress.Cellular and molecular life sciences : CMLS · 2026Article
- The Pro-Metastatic Roles of ROS.Antioxidants (Basel, Switzerland) · 2026Review
- Morphable 'Stitched' Sensors for Simultaneous Spatiotemporal Tracking of Correlated Bioanalytes in Living Cells.JACS Au · 2026Article
- Vacuolar ATPase regulates ureteric bud branching morphogenesis during kidney development.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Article
- Acidosis and the role of nanotechnology in mitigating cancer progression.Oncology reviews · 2026Review
- Role of the Dual-Specificity Phosphatase 6 (DUSP6) in the Activation of ERK1/2 Signaling by Hypoxia or Acidosis in Tumor Cells.Advances in experimental medicine and biology · 2026Article
- Data-Driven SustainableACS biomaterials science & engineering · 2025Article
- NIR pH-Responsive PEGylated PLGA Nanoparticles as Effective Phototoxic Agents in Resistant PDAC Cells.Polymers · 2025Article
- Acidosis-induced p38-kinase activation triggers an IL-6-mediated crosstalk of renal proximal tubule cells with fibroblasts leading to their inflammatory response.Cell communication and signaling : CCS · 2025Article
- Injectable carboxymethyl chitosan/oxidized dextran hydrogels containing zoledronic acid modified strontium hydroxyapatite nanoparticles.RSC advances · 2025Article
- Preparation and Characterization of Injectable Augmentation Gels Containing Polycaprolactone and Hyaluronic Acid.Journal of cosmetic dermatology · 2025Article
- Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer.Frontiers in cell and developmental biology · 2025Review
- Article
- pH-regulated single cell migration.Pflugers Archiv : European journal of physiology · 2024Review
- Crosstalk with renal proximal tubule cells drives acidosis-induced inflammatory response and dedifferentiation of fibroblasts via p38-singaling.Cell communication and signaling : CCS · 2024Article
- Metabolic Responses of Lung Adenocarcinoma Cells to Survive under Stressful Conditions Associated with Tumor Microenvironment.Metabolites · 2024Article
- Electrolysis products, reactive oxygen species and ATP loss contribute to cell death following irreversible electroporation with microsecond-long pulsed electric fields.Bioelectrochemistry (Amsterdam, Netherlands) · 2024Article
- Impact of Acute or Chronic Acidosis and Hypoxia on Gene Expression Patterns in Tumour Cells: Potential Functional Implications.Advances in experimental medicine and biology · 2024Article
- Involvement of the Transient Receptor Channels in Preclinical Models of Musculoskeletal Pain.Current neuropharmacology · 2024Review
13 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
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor micromilieu often shows pronounced acidosis forcing cells to adapt their phenotype towards enhanced tumorigenesis induced by altered cellular signalling and transcriptional regulation. In the presents study mechanisms and potential consequences of the crosstalk between extra- and intracellular pH (pH(e), pH(i)) and mitogen-activated-protein-kinases (ERK1/2, p38) was analyzed. Data were obtained mainly in AT1 R-3327 prostate carcinoma cells, but the principle importance was confirmed in 5 other cell types. Extracellular acidosis leads to a rapid and sustained decrease of pH(i) in parallel to p38 phosphorylation in all cell types and to ERK1/2 phosphorylation in 3 of 6 cell types. Furthermore, p38 phosphorylation was elicited by sole intracellular lactacidosis at normal pH(e). Inhibition of ERK1/2 phosphorylation during acidosis led to necrotic cell death. No evidence for the involvement of the kinases c-SRC, PKC, PKA, PI3K or EGFR nor changes in cell volume in acidosis-induced MAPK activation was obtained. However, our data reveal that acidosis enhances the formation of reactive oxygen species (ROS), probably originating from mitochondria, which subsequently trigger MAPK phosphorylation. Scavenging of ROS prevented acidosis-induced MAPK phosphorylation whereas addition of H(2)O(2) enhanced it. Finally, acidosis increased phosphorylation of the transcription factor CREB via p38, leading to increased transcriptional activity of a CRE-reporter even 24 h after switching the cells back to a normal environmental milieu. Thus, an acidic tumor microenvironment can induce a longer lasting p38-CREB-medited change in the transcriptional program, which may maintain the altered phenotype even when the cells leave the tumor environment.
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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.