ArticleScientific reports2016
Co-activation of AKT and c-Met triggers rapid hepatocellular carcinoma development via the mTORC1/FASN pathway in mice.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 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
84 citing papers in PubMed, 123 citations in OpenAlex.
- B7-H3 interaction with cMet enhances lipolysis to drive malignant progression of glioma via pSTAT3-ATGL axis.Journal of translational medicine · 2026Article
- INSIG1/2 succination mediated by the moonlighting function of ADSL promotes lipogenesis and liver tumorigenesis.Nature communications · 2026Article
- Amino acid metabolic reprogramming: future prospects for cholangiocarcinoma therapy.Cell death discovery · 2026Review
- Gene regulation through exon junction complex modularity.Nature structural & molecular biology · 2025Review
- HBx Drives Liver Cancer Stem Cell Generation Through Stimulating Glucose Metabolic Reprogramming.Journal of cellular and molecular medicine · 2025Article
- Targeting c-MET Alterations in Cancer: A Review of Genetic Drivers and Therapeutic Implications.Cancers · 2025Review
- ZDHHC20 mediated S-palmitoylation of fatty acid synthase (FASN) promotes hepatocarcinogenesis.Molecular cancer · 2024Article
- Oncogenic plasmid DNA and liver injury agent dictates liver cancer development in a mouse model.Clinical science (London, England : 1979) · 2024Article
- Preclinical Models of Hepatocellular Carcinoma: Current Utility, Limitations, and Challenges.Biomedicines · 2024Review
- Fatty Acid Synthase Promotes Hepatocellular Carcinoma Growth via S-Phase Kinase-Associated Protein 2/p27Medicina (Kaunas, Lithuania) · 2024Article
- Roles of Rictor alterations in gastrointestinal tumors (Review).Oncology reports · 2024Article
- Non-alcoholic fatty liver disease and diabetes mellitus as growing aetiologies of hepatocellular carcinoma.JHEP reports : innovation in hepatology · 2023Review
- Targeting EGFR/PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma.Pharmaceutics · 2023Review
- Loss of TP53 cooperates with c-MET overexpression to drive hepatocarcinogenesis.Cell death & disease · 2023Article
- The Role of PI3K/AKT/mTOR Signaling in Hepatocellular Carcinoma Metabolism.International journal of molecular sciences · 2023Review
- Targeted xCT-mediated Ferroptosis and Protumoral Polarization of Macrophages Is Effective against HCC and Enhances the Efficacy of the Anti-PD-1/L1 Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- microRNA-203 functions as a natural Ras inhibitor in hepatocellular carcinoma.American journal of cancer research · 2023Article
- Protein phosphatases regulate the liver microenvironment in the development of hepatocellular carcinoma.Experimental & molecular medicine · 2022Review
- Anti-cancer therapeutic strategies based on HGF/MET, EpCAM, and tumor-stromal cross talk.Cancer cell international · 2022Review
- Target Therapy for Hepatocellular Carcinoma: Beyond Receptor Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors.Biology · 2022Review
24 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
14 authors at 6 institutions in 4 countries.
Funding
Abstract
Activation of the AKT/mTOR cascade and overexpression of c-Met have been implicated in the development of human hepatocellular carcinoma (HCC). To elucidate the functional crosstalk between the two pathways, we generated a model characterized by the combined expression of activated AKT and c-Met in the mouse liver. Co-expression of AKT and c-Met triggered rapid liver tumor development and mice required to be euthanized within 8 weeks after hydrodynamic injection. At the molecular level, liver tumors induced by AKT/c-Met display activation of AKT/mTOR and Ras/MAPK cascades as well as increased lipogenesis and glycolysis. Since a remarkable lipogenic phenotype characterizes liver lesions from AKT/c-Met mice, we determined the requirement of lipogenesis in AKT/c-Met driven hepatocarcinogenesis using conditional Fatty Acid Synthase (FASN) knockout mice. Of note, hepatocarcinogenesis induced by AKT/c-Met was fully inhibited by FASN ablation. In human HCC samples, coordinated expression of FASN, activated AKT, and c-Met proteins was detected in a subgroup of biologically aggressive tumors. Altogether, our study demonstrates that co-activation of AKT and c-Met induces HCC development that depends on the mTORC1/FASN pathway. Suppression of mTORC1 and/or FASN might be highly detrimental for the growth of human HCC subsets characterized by concomitant induction of the AKT and c-Met cascades.
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.