ArticleEMBO reports2019
Oncogenic KRAS signaling activates mTORC1 through COUP-TFII-mediated lactate production.
Article in EMBO reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Review
- Mutant KRAS-driven selective mRNA translation reveals mechanisms and therapeutic vulnerabilities in cancer.Cell reports · 2026Article
- Lactate-driven pyrimidine synthesis promotes ferroptosis resistance in hepatocellular carcinoma.Molecular biomedicine · 2026Article
- Lactylation in cancer: metabolic mechanism and therapeutic strategies.Cell death discovery · 2025Review
- Glycolysis-mTORC1 crosstalk drives proliferation of patient-derived endometrial cancer spheroid cells with ALDH activity.Cell death discovery · 2024Article
- Iron regulatory protein 2 contributes to antimicrobial immunity by preserving lysosomal function in macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mechanism of targeting the mTOR pathway to regulate ferroptosis in NSCLC with different EGFR mutations.Oncology letters · 2024Article
- The current landscape of using direct inhibitors to target KRASExperimental hematology & oncology · 2023Review
- Cancer-associated fibroblasts reuse cancer-derived lactate to maintain a fibrotic and immunosuppressive microenvironment in pancreatic cancer.JCI insight · 2023Article
- Article
- MEK1-dependent MondoA phosphorylation regulates glucose uptake in response to ketone bodies in colorectal cancer cells.Cancer science · 2023Article
- Mutant KRAS Drives Immune Evasion by Sensitizing Cytotoxic T-Cells to Activation-Induced Cell Death in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Cancer-associated fibroblasts employ NUFIP1-dependent autophagy to secrete nucleosides and support pancreatic tumor growth.Nature cancer · 2022Article
- Targeting mTOR in the Context of Diet and Whole-body Metabolism.Endocrinology · 2022Review
- Differential expression analysis of genes and long non-coding RNAs associated with KRAS mutation in colorectal cancer cells.Scientific reports · 2022Article
- Blocking the Farnesyl Pocket of PDEδ Reduces Rheb-Dependent mTORC1 Activation and Survival ofFrontiers in pharmacology · 2022Article
- Oncogenic KRAS mutations enhance amino acid uptake by colorectal cancer cells via the hippo signaling effector YAP1.Molecular oncology · 2021Article
- Critical requirement of SOS1 RAS-GEF function for mitochondrial dynamics, metabolism, and redox homeostasis.Oncogene · 2021Article
- Metabolic Requirements for Spermatogonial Stem Cell Establishment and Maintenance In Vivo and In Vitro.International journal of molecular sciences · 2021Review
- Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis.PloS one · 2021Article
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic signals contribute to enhanced glycolysis and mTORC1 activity, leading to rapid cell proliferation in cancer. Regulation of glycolysis and mTORC1 by PI3K/Akt signaling is well established, but how KRAS-induced MEK signaling regulates these pathways remains poorly understood. Here, we report a role for MEK-driven lactate production in mTORC1 activation in KRAS-activated cells. KRAS/MEK-induced upregulation of the chicken ovalbumin upstream promoter transcriptional factor II (COUP-TFII) increases the expression of lactate dehydrogenase A (LDHA), resulting in lactate production and mTORC1 activation. Further, lactate inhibits the interaction of TSC2 and Rheb, leading to the cellular activation of mTORC1 irrespective of growth factor stimulation. These findings suggest that COUP-TFII is a novel oncogenic mediator, connecting KRAS signaling and glycolysis, and leading to mTORC1 activation and cellular growth.
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