ArticleBritish journal of cancer2020
Lactic acidosis induces resistance to the pan-Akt inhibitor uprosertib in colon cancer cells.
Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- Intracellular lactic acidosis reprograms glycolysis and mitochondrial anaplerosis in cancer cells.The Journal of biological chemistry · 2026Article
- Metabolic activation of LDHA by ERRα represses inflammasome-dependent pyroptosis and promotes ovarian cancer chemoresistance.Cell death & disease · 2026Article
- Immune cross talk and therapeutic advances in lactate metabolism in the tumor microenvironment (Review).Experimental and therapeutic medicine · 2026Review
- Review
- Beyond metabolism: exploring the regulatory and therapeutic implications of lactate and lactylation in cancer-regulated cell death.Cell death & disease · 2026Review
- Lactic Acid Drives ESM1 to Attenuate DNA Damage and CD8+ T Cell Infiltration in Cancer.Oncology research · 2026Article
- Targeting lactic acidosis in the tumor microenvironment: Enhancing TACE efficacy in hepatocellular carcinoma.Liver research (Beijing, China) · 2025Review
- Lactate and lactylation in cancer: drivers of immune suppression and microenvironmental reprogramming.Experimental hematology & oncology · 2025Review
- Review
- Breaking barriers: we need a multidisciplinary approach to tackle cancer drug resistance.BJC reports · 2025Review
- A method for the identification of lactate metabolism-related prognostic biomarkers and its validations in non-small cell lung cancer.Scientific reports · 2025Article
- Lactate and lactylation in cancer.Signal transduction and targeted therapy · 2025Review
- A Novel Prognostic Signature of Mitophagy-Related E3 Ubiquitin Ligases in Breast Cancer.International journal of molecular sciences · 2025Article
- Integrative multi-omics and machine learning identify a robust signature for discriminating prognosis and therapeutic targets in bladder cancer.Journal of Cancer · 2025Article
- Insights into recent findings and therapeutic potential of nonhistone lactylation in cancer.Frontiers in molecular biosciences · 2025Review
- The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities.Neoplasia (New York, N.Y.) · 2024Review
- Lactate helps cancer cells resist chemotherapy.Nature · 2024Article
- Article
- Membrane transporters in cell physiology, cancer metabolism and drug response.Disease models & mechanisms · 2023Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAkt signalling regulates glycolysis and drives the Warburg effect in cancer, thus decreased glucose utilisation is a pharmacodynamic marker of Akt inhibition. However, cancer cells can utilise alternative nutrients to glucose for energy such as lactate, which is often elevated in tumours together with increased acidity. We therefore hypothesised that lactic acidosis may confer resistance to Akt inhibition.
methodsThe effect of the pan-Akt inhibitor uprosertib (GSK2141795), on HCT116 and LS174T colon cancer cells was evaluated in the presence and absence of lactic acid in vitro. Expression of downstream Akt signalling proteins was determined using a phosphokinase array and immunoblotting. Metabolism was assessed using
resultsLactic acid-induced resistance to uprosertib was characterised by increased cell survival and reduced apoptosis. Uprosertib treatment reduced Akt signalling and glucose uptake irrespective of lactic acid supplementation. However, incorporation of lactate carbon and enhanced respiration was maintained in the presence of uprosertib and lactic acid. Inhibiting lactate transport or oxidative phosphorylation was sufficient to potentiate apoptosis in the presence of uprosertib.
conclusionsLactic acidosis confers resistance to uprosertib, which can be reversed by inhibiting lactate transport or oxidative metabolism.
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