ArticleGastroenterology2023
Dysregulated Amino Acid Sensing Drives Colorectal Cancer Growth and Metabolic Reprogramming Leading to Chemoresistance.
Article in Gastroenterology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 70 citations in OpenAlex.
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- Elesclomol-mediated cuproptosis overcomes cisplatin resistance by restricting epigenetically activated mitochondrial respiration: Novel therapeutic insights into cisplatin-elesclomol combination therapy.Acta pharmaceutica Sinica. B · 2026Article
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- RagC senses β-hydroxybutyrate abundancy to suppress mTORC1.Protein & cell · 2026Article
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- The MAPK/ATF3/ASNS axis drives amino acid metabolic reprogramming to promote NSCLC survival under glucose deprivation.Journal of translational medicine · 2026Article
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- Fibroblast-specificAmerican journal of physiology. Gastrointestinal and liver physiology · 2026Article
- Arginine dependency in omental metastasis of epithelial ovarian cancer reveals a therapeutic vulnerability.Cell death & disease · 2026Article
- Colorimetric detection of amino acids enabled by functional nanomaterials: mechanisms, performance evaluation, and translational perspectives.Mikrochimica acta · 2026Review
- Bifidobacterium breve inhibits colorectal cancer via extracellular vesicles containing formate acetyltransferase.Journal of nanobiotechnology · 2026Article
- Mechanism of isoleucyl-tRNA synthetase 2 regulating proliferation and apoptosis of cervical cancer cells.Scientific reports · 2026Article
- RPS6KA1 Remodels Fatty Acid Metabolism and Suppresses Malignant Progression in Colorectal Cancer.Biomedicines · 2026Article
- Impaired nitrogenous waste clearance promotes hepatocellular carcinoma.Science advances · 2026Article
- Comment on "α-hederin decreases the glycolysis level in intestinal epithelial cells via SNX10-mediated DEPDC5 degradation".Journal of pharmaceutical analysis · 2026Article
- Beyond Glucose and Lipids: The Pivotal Role of Amino Acid Reprogramming in Shaping the Tumor Microenvironment and Guiding the Development of Novel Therapeutics.International journal of medical sciences · 2026Review
- Mechanisms of mTORC1 and GCN2 amino acid sensing pathways in tumorigenesis and metastatic progression (Review).International journal of molecular medicine · 2026Review
- GATOR1 complex controls cisplatin sensitivity.Cell death & disease · 2025Article
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Intestinal amino acid metabolic response and its roles in inflammatory bowel disease.Cell communication and signaling : CCS · 2025Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsColorectal cancer (CRC) is a devastating disease that is highly modulated by dietary nutrients. Mechanistic target of rapamycin complex 1 (mTORC1) contributes to tumor growth and limits therapy responses. Growth factor signaling is a major mechanism of mTORC1 activation. However, compensatory pathways exist to sustain mTORC1 activity after therapies that target oncogenic growth factor signaling. Amino acids potently activate mTORC1 via amino acid-sensing GTPase activity towards Rags (GATOR). The role of amino acid-sensing pathways in CRC is unclear.
methodsHuman colon cancer cell lines, preclinical intestinal epithelial-specific GATOR1 and GATOR2 knockout mice subjected to colitis-induced or sporadic colon tumor models, small interfering RNA screening targeting regulators of mTORC1, and tissues of patients with CRC were used to assess the role of amino acid sensing in CRC.
resultsWe identified loss-of-function mutations of the GATOR1 complex in CRC and showed that altered expression of amino acid-sensing pathways predicted poor patient outcomes. We showed that dysregulated amino acid-sensing induced mTORC1 activation drives colon tumorigenesis in multiple mouse models. We found amino acid-sensing pathways to be essential in the cellular reprogramming of chemoresistance, and chemotherapeutic-resistant patients with colon cancer exhibited de-regulated amino acid sensing. Limiting amino acids in in vitro and in vivo models (low-protein diet) reverted drug resistance, revealing a metabolic vulnerability.
conclusionsOur findings suggest a critical role for amino acid-sensing pathways in driving CRC and highlight the translational implications of dietary protein intervention in CRC.
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