Evidence map›Paper›PMID 26476289›Full record

ArticleJournal of hepatology2016

Inactivation of fatty acid synthase impairs hepatocarcinogenesis driven by AKT in mice and humans.

Lei Li, Giulia M Pilo, Xiaolei Li, Antonio Cigliano, Gavinella Latte, Li Che, Christy Joseph, Marta Mela, Chunmei Wang, Lijie Jiang and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of hepatology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
3.9field-weighted citation impact, top 6% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

89 citing papers in PubMed, 151 citations in OpenAlex.

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  15. Ficolin 3 promotes ferroptosis in HCC by downregulating IR/SREBP axis-mediated MUFA synthesis.Journal of experimental & clinical cancer research : CR · 2024
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29 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 4 countries.

Lei LiSchool of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Giulia M PiloDepartment of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
Xiaolei LiDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA; Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.
Antonio CiglianoInstitut für Pathologie, Universitätsmedizin Greifswald, Greifswald, Germany.
Gavinella LatteDepartment of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
Li CheDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Christy JosephInstitut für Pathologie, Universitätsmedizin Greifswald, Greifswald, Germany.
Marta MelaDepartment of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
Chunmei WangDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Lijie JiangDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Silvia RibbackInstitut für Pathologie, Universitätsmedizin Greifswald, Greifswald, Germany.
Maria M SimileDepartment of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
Rosa M PascaleDepartment of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy.
Frank DombrowskiInstitut für Pathologie, Universitätsmedizin Greifswald, Greifswald, Germany.
Matthias EvertInstitut für Pathologie, Universitätsmedizin Greifswald, Greifswald, Germany.
Clay F SemenkovichDivision of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, St. Louis, MO, USA.
Xin ChenDepartment of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA.
Diego F CalvisiDepartment of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy. Electronic address: calvisid@uniss.it.
University of Sassari · ITUniversitätsmedizin Greifswald · DEUniversity of California, San Francisco · USHuazhong University of Science and Technology · CNWashington University in St. Louis · US

Funding

UCSF Liver Core CenterP30DK026743 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Holger Willenbring · 1986 to 2026
$30.7M
Molecular Genetics of Liver CancersR01CA136606 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHEN, XIN · 2009 to 2016
$2.6M
Lipogenic inhibitors in prevention of oncogene induced liver cancerR03CA165122 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHEN, XIN · 2012 to 2013
$150k
NCI NIH HHS R01 CA136606NCI NIH HHS R01CA136606NCI NIH HHS R03 CA165122NCI NIH HHS R03CA165122NIDDK NIH HHS P30 DK026743NIDDK NIH HHS P30DK026743
6 · The paper itself

Abstract

BACKGROUND &

aimsCumulating evidence underlines the crucial role of aberrant lipogenesis in human hepatocellular carcinoma (HCC). Here, we investigated the oncogenic potential of fatty acid synthase (FASN), the master regulator of de novo lipogenesis, in the mouse liver.

methodsFASN was overexpressed in the mouse liver, either alone or in combination with activated N-Ras, c-Met, or SCD1, via hydrodynamic injection. Activated AKT was overexpressed via hydrodynamic injection in livers of conditional FASN or Rictor knockout mice. FASN was suppressed in human hepatoma cell lines via specific small interfering RNA.

resultsOverexpression of FASN, either alone or in combination with other genes associated with hepatocarcinogenesis, did not induce histological liver alterations. In contrast, genetic ablation of FASN resulted in the complete inhibition of hepatocarcinogenesis in AKT-overexpressing mice. In human HCC cell lines, FASN inactivation led to a decline in cell proliferation and a rise in apoptosis, which were paralleled by a decrease in the levels of phosphorylated/activated AKT, an event controlled by the mammalian target of rapamycin complex 2 (mTORC2). Downregulation of AKT phosphorylation/activation following FASN inactivation was associated with a strong inhibition of rapamycin-insensitive companion of mTOR (Rictor), the major component of mTORC2, at post-transcriptional level. Finally, genetic ablation of Rictor impaired AKT-driven hepatocarcinogenesis in mice.

conclusionsFASN is not oncogenic per se in the mouse liver, but is necessary for AKT-driven hepatocarcinogenesis. Pharmacological blockade of FASN might be highly useful in the treatment of human HCC characterized by activation of the AKT pathway.

Indexed as

CarcinogenesisCarcinoma, HepatocellularFatty Acid Synthase, Type ILiver NeoplasmsAnimalsApoptosisCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansLiverMicePhosphorylationProto-Oncogene Proteins c-aktSignal TransductionFASN protein, humanFatty Acid Synthase, Type IProto-Oncogene Proteins c-aktAKTFatty acid synthaseHepatocellular carcinomaLipogenesisRictor

Identifiers

PMID26476289
PMCPMC4718802
OpenAlexW2097365930

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.