ArticleMolecular oncology2021
Oncogenic KRAS mutations enhance amino acid uptake by colorectal cancer cells via the hippo signaling effector YAP1.
Article in Molecular oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 53 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- The Crosstalk Between YAP/TAZ and Cancer Metabolism: From Mechanistic Insights to Drug Discovery.International journal of molecular sciences · 2026Review
- Article
- Genetic mutations governing ferroptosis sensitivity and resistance: a precision approach to cancer therapy.Cell death & disease · 2026Review
- Targeting glutamine metabolism to modulate macrophage functions in the tumor microenvironment.Discover oncology · 2026Review
- YAP1 in control: how RNA networks and protein modifications shape its function and therapeutic targetability.Molecular cancer · 2026Review
- Glutamine promotes acute wound healing by mediating glutamine metabolism and M2 macrophage polarization via the MEK/ERK/SLC1A5 signaling pathway.Scientific reports · 2026Article
- A comprehensive review of mechanisms underlying resistance to immune checkpoint inhibitors.Frontiers in immunology · 2026Review
- Metabolic adaptations in cancer progression.Physiological reviews · 2026Review
- Inhibition of apoptosis in breast cancer cells by si-FoxO3a through the protein digestion and absorption signaling pathway.Oncology letters · 2025Article
- TXNIP mediates LAT1/SLC7A5 endocytosis to limit amino acid uptake in cells entering quiescence.The EMBO journal · 2025Article
- Redox-Amino Acid Metabolic Crosstalk in Ovarian Cancer Stem Cells: Integrating Metabolic Reprogramming, Signaling, and the Tumor Microenvironment.Antioxidants (Basel, Switzerland) · 2025Review
- Astatine-211-Labeled Therapy Targeting Amino Acid Transporters: Overcoming Drug Resistance in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2025Review
- Glutaminase inhibitor CB-839 causes metabolic adjustments in colorectal cancer cells.Scientific reports · 2025Article
- Glutamine: a new strategy for targeted metabolic therapy in the tumor microenvironment.Cell death discovery · 2025Review
- Novel paradigms in KRAS targeting: Unveiling strategies to combat drug resistance.Chinese medical journal · 2025Review
- Targeting glutamine metabolism as a potential target for cancer treatment.Journal of experimental & clinical cancer research : CR · 2025Review
- Learning the therapeutic targets of acute myeloid leukemia through multiscale human interactome network and community analysis.BioData mining · 2025Article
- The roles of KRAS in cancer metabolism, tumor microenvironment and clinical therapy.Molecular cancer · 2025Review
- The metabolism-immune axis in colorectal cancer: remodeling the tumor microenvironment through metabolite signaling.Frontiers in immunology · 2025Review
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncogenic KRAS mutations develop unique metabolic dependencies on nutrients to support tumor metabolism and cell proliferation. In particular, KRAS mutant cancer cells exploit amino acids (AAs) such as glutamine and leucine, to accelerate energy metabolism, redox balance through glutathione synthesis and macromolecule biosynthesis. However, the identities of the amino acid transporters (AATs) that are prominently upregulated in KRAS mutant cancer cells, and the mechanism regulating their expression have not yet been systematically investigated. Here, we report that the majority of the KRAS mutant colorectal cancer (CRC) cells upregulate selected AATs (SLC7A5/LAT1, SLC38A2/SNAT2, and SLC1A5/ASCT2), which correlates with enhanced uptake of AAs such as glutamine and leucine. Consistently, knockdown of oncogenic KRAS downregulated the expression of AATs, thereby decreasing the levels of amino acids taken up by CRC cells. Moreover, overexpression of mutant KRAS upregulated the expression of AATs (SLC7A5/LAT1, SLC38A2/SNAT2, and SLC1A5/ASCT2) in KRAS wild-type CRC cells and mouse embryonic fibroblasts. In addition, we show that the YAP1 (Yes-associated protein 1) transcriptional coactivator accounts for increased expression of AATs and mTOR activation in KRAS mutant CRC cells. Specific knockdown of AATs by shRNAs or pharmacological blockage of AATs effectively inhibited AA uptake, mTOR activation, and cell proliferation. Collectively, we conclude that oncogenic KRAS mutations enhance the expression of AATs via the hippo effector YAP1, leading to mTOR activation and CRC cell proliferation.
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