ArticleHepatology (Baltimore, Md.)2017
A functional mammalian target of rapamycin complex 1 signaling is indispensable for c-Myc-driven hepatocarcinogenesis.
Article in Hepatology (Baltimore, Md.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
126 citing papers in PubMed, 194 citations in OpenAlex.
- Molecular Pathophysiology of Hepatocellular Carcinoma: From Metabolic Inflammation to Therapeutic Targets.Cancers · 2026Review
- Targeting the 4EBP1/HSP90β/Nrf2 Axis Sensitizes β-catenin-mutant Hepatocellular Carcinoma to mTOR Inhibitors via Ferroptosis Induction.Journal of clinical and translational hepatology · 2026Article
- Targeting glutamine metabolism to modulate macrophage functions in the tumor microenvironment.Discover oncology · 2026Review
- A Very-low-energy Fast Involves Increased Adipose Inflammatory Gene Expression: A 6-day Feeding Trial (FASTOMICS-6).The Journal of clinical endocrinology and metabolism · 2026Article
- The UFM1 Conjugation System: A Master Regulator of Cellular Stress Surveillance in Human Disease.Biology · 2026Review
- Notch-1 suppressed vascular dementia via modulating AMPK/mTOR/TFEB/YAP signaling induced ferroptosis.European journal of medical research · 2026Article
- Distinct sensing of BCAAs by mTOR and c-Myc governs T cell proliferation, independent of catabolism.bioRxiv : the preprint server for biology · 2026Article
- Arginine Transporters in Human Cancers: Emerging Mechanisms and Clinical Implications.Biomolecules · 2026Review
- Lysophosphatidic acid-induced Arf6-driven macropinocytosis of CD147International journal of biological sciences · 2026Article
- ARMH4 accelerates aging by maintaining a positive-feedback growth signaling circuit.Nature communications · 2025Article
- Recent insights into the roles and therapeutic potentials of GLS1 in inflammatory diseases.Journal of pharmaceutical analysis · 2025Review
- Targeting the hepatic circadian clock concomitant with tyrosine kinase inhibition reverses late-stage hepatocellular carcinoma.Cell reports · 2025Article
- Unraveling the role of the solute carrier family in hepatocellular carcinoma: mechanisms and therapeutic prospects.Cancer cell international · 2025Review
- Transcription factor activator protein 4 (AP4)-mediated intrinsic control of axon regeneration.Science advances · 2025Article
- Chemoprevention of hepatocellular carcinoma using N-acetylgalactosamine-conjugated siRNAs.Disease models & mechanisms · 2025Article
- RBM39 promotes hepatocarcinogenesis by regulating RFX1's alternative splicing and subsequent activation of integrin signaling pathway.Oncogene · 2025Article
- Molecular Alterations in Gastric Intestinal Metaplasia Shed Light on Alteration of Methionine Metabolism: Insight into New Diagnostic and Treatment Approaches.Biomedicines · 2025Review
- Muscle fiber Myc is dispensable for muscle growth and its forced expression severely perturbs homeostasis.Nature communications · 2025Article
- MAF1 inhibits hepatocarcinogenesis by fostering an immunostimulatory tumor microenvironment.Journal for immunotherapy of cancer · 2025Article
- Metabolic Signaling in the Tumor Microenvironment.Cancers · 2025Review
66 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 8 institutions in 4 countries.
Funding
Abstract
Amplification and/or activation of the c-Myc proto-oncogene is one of the leading genetic events along hepatocarcinogenesis. The oncogenic potential of c-Myc has been proven experimentally by the finding that its overexpression in the mouse liver triggers tumor formation. However, the molecular mechanism whereby c-Myc exerts its oncogenic activity in the liver remains poorly understood. Here, we demonstrate that the mammalian target of rapamycin complex 1 (mTORC1) cascade is activated and necessary for c-Myc-dependent hepatocarcinogenesis. Specifically, we found that ablation of Raptor, the unique member of mTORC1, strongly inhibits c-Myc liver tumor formation. Also, the p70 ribosomal S6 kinase/ribosomal protein S6 and eukaryotic translation initiation factor 4E-binding protein 1/eukaryotic translation initiation factor 4E signaling cascades downstream of mTORC1 are required for c-Myc-driven tumorigenesis. Intriguingly, microarray expression analysis revealed up-regulation of multiple amino acid transporters, including solute carrier family 1 member A5 (SLC1A5) and SLC7A6, leading to robust uptake of amino acids, including glutamine, into c-Myc tumor cells. Subsequent functional studies showed that amino acids are critical for activation of mTORC1 as their inhibition suppressed mTORC1 in c-Myc tumor cells. In human hepatocellular carcinoma specimens, levels of c-Myc directly correlate with those of mTORC1 activation as well as of SLC1A5 and SLC7A6.
conclusionOur current study indicates that an intact mTORC1 axis is required for c-Myc-driven hepatocarcinogenesis; thus, targeting the mTOR pathway or amino acid transporters may be an effective and novel therapeutic option for the treatment of hepatocellular carcinoma with activated c-Myc signaling. (Hepatology 2017;66:167-181).
Indexed as
Identifiers
What OpenQuestion holds
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.