ArticleOncotarget2015
5-fluorouracil resistant colon cancer cells are addicted to OXPHOS to survive and enhance stem-like traits.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 153 citations in OpenAlex.
- Proteogenomic Analysis of HDAC4 and HDAC5 in Uveal Melanoma.Molecular medicine (Cambridge, Mass.) · 2026Article
- Cancer Stem Cell Quiescence: Molecular and Microenvironmental Evidence for an Actively Regulated Adaptive Survival Strategy.Cancer medicine · 2026Review
- JI-CS004, a chloroform fraction of SH003, induces reactive oxygen species-dependent intrinsic apoptosis via endoplasmic reticulum stress-associated mitochondrial dysfunction in human colorectal cancer cells.Molecular biology reports · 2026Article
- Mitochondrial metabolism determines chemotherapy sensitivity in colorectal cancer.Nature metabolism · 2026Article
- Repurposed cAMP-Modulating Agents Enhance 5-Fluorouracil Response Through Membrane-Dependent Mechanisms.Membranes · 2026Review
- Tumor mitochondrial respiration rather than glycolytic activity predicts recurrence in colorectal cancer: an ex vivo bioenergetic profiling study.BMC gastroenterology · 2026Article
- Review
- Metabotherapy for intestinal disease: using metabolites to prevent and treat disorders of the gut.Nature reviews. Gastroenterology & hepatology · 2026Review
- FGFR3 oncogenic activation drives oxidative metabolic reprogramming in bladder cancer: a systems metabolomics approach.Communications biology · 2026Article
- ASCC3 promotes chemosensitivity in colorectal cancer cells.Scientific reports · 2026Article
- Tumor metabolic adaptation induced by L-asparaginase reveals a vulnerability to PARP1/2 inhibitor in B-cell lymphomas.Nature communications · 2026Article
- Convergent adaptive architectures linking chemoresistance and radioresistance in chemoradiotherapy: a systems-level perspective.Frontiers in oncology · 2026Review
- Mechanistic role of glycolytic pathways in the tumor microenvironment in driving chemoresistance.Frontiers in cell and developmental biology · 2026Review
- Mitochondria: from powerhouses of cells to hubs in antitumor immunity.Frontiers in immunology · 2026Review
- PPA1 promotes oxidative phosphorylation and malignant progression of colorectal cancer under glucose restriction via AMPK/ULK1/FUNDC1-mediated mitophagy.Cell death discovery · 2025Article
- Metformin's multifaceted role in colorectal cancer: mechanisms of action and synergy with standard treatments.Discover oncology · 2025Review
- Engineering Inorganic Nanoparticles to Induce Cuproptosis: A New Strategy for Cancer Therapy.Pharmaceutics · 2025Review
- Genetic and transcriptomic alterations underlying aggressiveness in 5-fluorouracil-resistant HCT116 cells.Medical oncology (Northwood, London, England) · 2025Article
- Protein lipoylation in cancer: metabolic reprogramming and therapeutic potential.Cell death discovery · 2025Review
- PHGDH drives 5-FU chemoresistance in colorectal cancer through the Hedgehog signaling.Journal of experimental & clinical cancer research : CR · 2025Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Despite marked tumor shrinkage after 5-FU treatment, the frequency of colon cancer relapse indicates that a fraction of tumor cells survives treatment causing tumor recurrence. The majority of cancer cells divert metabolites into anabolic pathways through Warburg behavior giving an advantage in terms of tumor growth. Here, we report that treatment of colon cancer cell with 5-FU selects for cells with mesenchymal stem-like properties that undergo a metabolic reprogramming resulting in addiction to OXPHOS to meet energy demands. 5-FU treatment-resistant cells show a de novo expression of pyruvate kinase M1 (PKM1) and repression of PKM2, correlating with repression of the pentose phosphate pathway, decrease in NADPH level and in antioxidant defenses, promoting PKM2 oxidation and acquisition of stem-like phenotype. Response to 5-FU in a xenotransplantation model of human colon cancer confirms activation of mitochondrial function. Combined treatment with 5-FU and a pharmacological inhibitor of OXPHOS abolished the spherogenic potential of colon cancer cells and diminished the expression of stem-like markers. These findings suggest that inhibition of OXPHOS in combination with 5-FU is a rational combination strategy to achieve durable treatment response in colon cancer.
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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.