ArticlePLoS genetics2008
The genomic analysis of lactic acidosis and acidosis response in human cancers.
Article in PLoS genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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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.
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Who cites it
128 citing papers in PubMed, 215 citations in OpenAlex.
- Trial
- No evident dose-response relationship between cellular ROS level and its cytotoxicity--a paradoxical issue in ROS-based cancer therapy.Scientific reports · 2014Trial
- Molecular Mechanisms and Immune Regulation in Prostate Cancer: A Review.International journal of molecular sciences · 2026Review
- Acidosis-associated gene signature defines novel subtypes and dual-target therapeutic candidates in breast cancer.Journal of translational medicine · 2026Article
- Hypoxic CA9 variant as a potential prognostic marker in gastric and breast cancers.Scientific reports · 2026Article
- Dysregulated metabolic homeostasis as a unifying death mechanism underlying the diverse clinical manifestations of COVID-19: insights from a retrospective analysis of sequential blood variables.Frontiers in medicine · 2026Article
- The molecular axis hnRNPU/circKCNK2/EDC4/IL-11 aggravates osteolytic bone metastasis of RCC.Oncogene · 2025Article
- Resistance to neoadjuvant chemotherapy in breast cancers: a metabolic perspective.Journal of experimental & clinical cancer research : CR · 2025Review
- Oxidative and Glycolytic Metabolism: Their Reciprocal Regulation and Dysregulation in Cancer.Cells · 2025Review
- What's on the menu?: metabolic constraints in the pancreatic tumor microenvironment.The Journal of clinical investigation · 2025Review
- Phenotypic screen of sixty-eight colorectal cancer cell lines identifies CEACAM6 and CEACAM5 as markers of acid resistance.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Bridging the gap: advancing cancer cell culture to reveal key metabolic targets.Frontiers in oncology · 2024Review
- Cepharanthine, a regulator of keap1-Nrf2, inhibits gastric cancer growth through oxidative stress and energy metabolism pathway.Cell death discovery · 2023Article
- Environmental Determinants of Ferroptosis in Cancer.Cancers · 2023Review
- Functional Imaging of Hypoxia: PET and MRI.Cancers · 2023Review
- Review
- How Warburg-Associated Lactic Acidosis Rewires Cancer Cell Energy Metabolism to Resist Glucose Deprivation.Cancers · 2023Review
- The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism.International journal of molecular sciences · 2023Review
- Synergistic cytotoxicity of perifosine and ABT-737 to colon cancer cells.Journal of cellular and molecular medicine · 2023Article
- Alteration of Cellular Energy Metabolism through LPAR2-Axin2 Axis in Gastric Cancer.Biomolecules · 2022Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The tumor microenvironment has a significant impact on tumor development. Two important determinants in this environment are hypoxia and lactic acidosis. Although lactic acidosis has long been recognized as an important factor in cancer, relatively little is known about how cells respond to lactic acidosis and how that response relates to cancer phenotypes. We develop genome-scale gene expression studies to dissect transcriptional responses of primary human mammary epithelial cells to lactic acidosis and hypoxia in vitro and to explore how they are linked to clinical tumor phenotypes in vivo. The resulting experimental signatures of responses to lactic acidosis and hypoxia are evaluated in a heterogeneous set of breast cancer datasets. A strong lactic acidosis response signature identifies a subgroup of low-risk breast cancer patients having distinct metabolic profiles suggestive of a preference for aerobic respiration. The association of lactic acidosis response with good survival outcomes may relate to the role of lactic acidosis in directing energy generation toward aerobic respiration and utilization of other energy sources via inhibition of glycolysis. This "inhibition of glycolysis" phenotype in tumors is likely caused by the repression of glycolysis gene expression and Akt inhibition. Our study presents a genomic evaluation of the prognostic information of a lactic acidosis response independent of the hypoxic response. Our results identify causal roles of lactic acidosis in metabolic reprogramming, and the direct functional consequence of lactic acidosis pathway activity on cellular responses and tumor development. The study also demonstrates the utility of genomic analysis that maps expression-based findings from in vitro experiments to human samples to assess links to in vivo clinical phenotypes.
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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.