ArticleOncotarget2014
Acidosis promotes invasiveness of breast cancer cells through ROS-AKT-NF-κB pathway.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 91 citations in OpenAlex.
- Article
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- Targeting phosphofructokinase in cancer: integrating natural products for metabolic reprogramming and therapeutic innovation.Frontiers in pharmacology · 2026Review
- Loss of YTHDF1 suppresses the progression of malignant rhabdoid tumor of the kidney by regulating Glutathione S-transferase Mu 2 (GSTM2).Cell biology and toxicology · 2025Article
- The Use of Patient-Derived Organoids in the Study of Molecular Metabolic Adaptation in Breast Cancer.International journal of molecular sciences · 2024Review
- Targeting the Warburg Effect in Cancer: Where Do We Stand?International journal of molecular sciences · 2024Review
- Clinical significance of acidic extracellular microenvironment modulated genes.Frontiers in oncology · 2024Article
- Immunotherapy Enhancement by Targeting Extracellular Tumor pH in Triple-Negative Breast Cancer Mouse Model.Cancers · 2023Article
- Anticancer Effect of Gallic Acid on Acidity-Induced Invasion of MCF7 Breast Cancer Cells.Nutrients · 2023Article
- NF-κB mediated regulation of tumor cell proliferation in hypoxic microenvironment.Frontiers in pharmacology · 2023Review
- Genome-wide association study of mammary gland tumors in Maltese dogs.Frontiers in veterinary science · 2023Article
- Enhancers regulate 3' end processing activity to control expression of alternative 3'UTR isoforms.Nature communications · 2022Article
- Identification of distinct slow mode of reversible adaptation of pancreatic ductal adenocarcinoma to the prolonged acidic pH microenvironment.Journal of experimental & clinical cancer research : CR · 2022Article
- Piperlongumine, a piper alkaloid, enhances the efficacy of doxorubicin in breast cancer: involvement of glucose import, ROS, NF-κB and lncRNAs.Apoptosis : an international journal on programmed cell death · 2022Article
- Dietary Acid Load, Serum Polychlorinated Biphenyl Levels, and Mortality Following Breast Cancer in the Long Island Breast Cancer Study Project.International journal of environmental research and public health · 2021Article
- Phosphoenolpyruvate Carboxykinase (PCK) in the Brain Gluconeogenic Pathway Contributes to Oxidative and Lactic Injury After Stroke.Molecular neurobiology · 2021Article
- The metabolism of cancer cells during metastasis.Nature reviews. Cancer · 2021Review
- Effects of the Tumor Environment on Ion Channels: Implication for Breast Cancer Progression.Reviews of physiology, biochemistry and pharmacology · 2021Review
- The Molecular Effects of Dietary Acid Load on Metabolic Disease (The Cellular PasaDoble: The Fast-Paced Dance of pH Regulation).Frontiers in molecular medicine · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
It is well known that acidic microenvironment promotes tumorigenesis, however, the underlying mechanism remains largely unknown. In the present study, we show that acidosis promotes invasiveness of breast cancer cells through a series of signaling events. First, our study indicates that NF-κB is a key factor for acidosis-induced cell invasion. Acidosis activates NF-κB without affecting STAT3 activity; knockdown of NF-κB p65 abrogates the acidosis-induced invasion activity. Next, we show that the activation of NF-κB is mediated through phosphorylation and degradation of IκBα; and phosphorylation and nuclear translocation of p65. Upstream to NF-κB signaling, AKT is activated under acidic conditions. Moreover, acidosis induces generation of reactive oxygen species (ROS) which can be suppressed by ROS scavengers, reversing the acidosis-induced activation of AKT and NF-κB, and invasiveness. As a negative regulator of AKT, PTEN is oxidized and inactivated by the acidosis-induced ROS. Finally, inhibition of NADPH oxidase (NOX) suppresses acidosis-induced ROS production, suggesting involvement of NOX in acidosis-induced signaling cascade. Of considerable interest, acidosis-induced ROS production and activation of AKT and NF-κB can be only detected in cancer cells, but not in non-malignant cells. Together, these results demonstrate a cancer specific acidosis-induced signaling cascade in breast cancer cells, leading to cell invasion.
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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.