ArticleCancer & metabolism2019
Inhibition of phosphoenolpyruvate carboxykinase blocks lactate utilization and impairs tumor growth in colorectal cancer.
Article in Cancer & metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 54 citations in OpenAlex.
- The proteomic landscape of small urinary extracellular vesicles during kidney transplantation.Journal of extracellular vesicles · 2020Trial
- Metabolic reprogramming in colorectal cancer: Mechanisms and therapeutic insights.Genes & diseases · 2027Review
- Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Lactate metabolism and protein lactylation in colorectal cancer: from metabolic reprogramming to epigenetic regulation.Frontiers in oncology · 2026Review
- Glucose and Lactate, Starters or Intermediates of Cancer Metabolic Rewiring.Advances in experimental medicine and biology · 2026Review
- Functional genomics reveals strain-specific genetic requirements conferring hypoxic growth ineLife · 2025Article
- Raman Spectroscopy of Cell-Free Cervicovaginal Lavage for HPV Lesion Diagnosis: A Pilot Study.International journal of molecular sciences · 2025Article
- Targeting pyruvate metabolism generates distinct CD8+ T cell responses to gammaherpesvirus and B lymphoma.JCI insight · 2025Article
- Guanine monophosphate synthase-mediated nuclear and mitochondrial communication in the progression of gastric cancer.Translational cancer research · 2025Article
- Glycogenesis and glyconeogenesis from glutamine, lactate and glycerol support human macrophage functions.EMBO reports · 2024Article
- High sugar diet promotes tumor progression paradoxically through aberrant upregulation of pepck1.Cellular and molecular life sciences : CMLS · 2024Article
- Comparative transcriptomic and phenotypic analysis of induced pluripotent stem cell hepatocyte-like cells and primary human hepatocytes.Cell and tissue research · 2024Article
- Serine synthesis and catabolism in starved lung cancer and primary bronchial epithelial cells.Cancer & metabolism · 2024Article
- B7-H3 at the crossroads between tumor plasticity and colorectal cancer progression: a potential target for therapeutic intervention.Cancer metastasis reviews · 2024Review
- Tumor glucose metabolism and the T cell glycocalyx: implication for T cell function.Frontiers in immunology · 2024Review
- Emerging roles of cytosolic phosphoenolpyruvate kinase 1 (PCK1) in cancer.Biochemistry and biophysics reports · 2023Review
- How Warburg-Associated Lactic Acidosis Rewires Cancer Cell Energy Metabolism to Resist Glucose Deprivation.Cancers · 2023Review
- Mitochondrial phosphoenolpyruvate carboxykinase inhibits kidney renal clear cell carcinoma malignant progression, leading to cell energy metabolism imbalance.American journal of cancer research · 2023Article
- Disruptor of telomeric silencing 1-like promotes ovarian cancer tumor growth by stimulating pro-tumorigenic metabolic pathways and blocking apoptosis.Oncogenesis · 2021Article
- Mechanisms of Metabolic Reprogramming in Cancer Cells Supporting Enhanced Growth and Proliferation.Cells · 2021Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetabolic reprogramming is a key feature of malignant cells. While glucose is one of the primary substrates for malignant cells, cancer cells also display a remarkable metabolic flexibility. Depending on nutrient availability and requirements, cancer cells will utilize alternative fuel sources to maintain the TCA cycle for bioenergetic and biosynthetic requirements. Lactate was typically viewed as a passive byproduct of cancer cells. However, studies now show that lactate is an important substrate for the TCA cycle in breast, lung, and pancreatic cancer.
methodsMetabolic analysis of colorectal cancer (CRC) cells was performed using a combination of bioenergetic analysis and
resultsWe show here that CRC cells use lactate to fuel the TCA cycle and promote growth especially under nutrient-deprived conditions. This was mediated in part by maintaining cellular bioenergetics. Therefore targeting the ability of cancer cells to utilize lactate via the TCA cycle would have a significant therapeutic benefit. Phosphoenolpyruvate carboxykinase (PEPCK) is an important cataplerotic enzyme that promotes TCA cycle activity in CRC cells. Treatment of CRC cells with low micromolar doses of a PEPCK inhibitor (PEPCKi) developed for diabetes decreased cell proliferation and utilization of lactate by the TCA cycle in vitro and in vivo. Mechanistically, we observed that the PEPCKi increased nutrient stress as determined by decreased cellular bioenergetics including decreased respiration, ATP levels, and increased AMPK activation.
conclusionsThese studies highlight lactate as an important substrate for CRC and the use of PEPCKi as a therapeutic approach to target lactate utilization in CRC cells.
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