Evidence map›Paper›PMID 30244972›Full record

ArticleCell metabolism2019

Inhibition of Acetyl-CoA Carboxylase by Phosphorylation or the Inhibitor ND-654 Suppresses Lipogenesis and Hepatocellular Carcinoma.

James S V Lally, Sarani Ghoshal, Danielle K DePeralta, Omeed Moaven, Lan Wei, Ricard Masia, Derek J Erstad, Naoto Fujiwara, Vivian Leong, Vanessa P Houde and 25 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 250 papers.

0numbers the graph read from it
0cells of the map it votes in
250citing papers in PubMed
10.1field-weighted citation impact, top 1% 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

250 citing papers in PubMed, 403 citations in OpenAlex.

  1. Review
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  7. Advances in Lipid Metabolism Reprogramming in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2026
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190 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

35 authors at 8 institutions in 2 countries.

James S V LallyDepartment of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada.
Sarani GhoshalDivison of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
Danielle K DePeraltaDivison of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
Omeed MoavenDivison of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
Lan WeiDivison of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
Ricard MasiaDepartment of Pathology, Massachusetts General Hospital Cancer Center and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
Derek J ErstadDivison of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
Naoto FujiwaraLiver Tumor Translational Research Program, Harold C. Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Vivian LeongDepartment of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada.
Vanessa P HoudeDepartment of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada; Department of Oncology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4L8, Canada.
Alexander E AnagnostopoulosDepartment of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada.
Alice WangDepartment of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada.
Lindsay A BroadfieldDepartment of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada.
Rebecca J FordDepartment of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada.
Robert A FosterDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, ON NIG 2W1, Canada.
Jamie BatesGilead Sciences, Foster City, CA 94404, USA.
Hailing SunGilead Sciences, Foster City, CA 94404, USA.
Ting WangGilead Sciences, Foster City, CA 94404, USA.
Henry LiuGilead Sciences, Foster City, CA 94404, USA.
Adrian S RayGilead Sciences, Foster City, CA 94404, USA.
Asish K SahaDepartment of Medicine and Physiology, School of Medicine, Endocrinology, Diabetes, and Nutrition, Boston University, Boston, MA 02118, USA.
Jeremy GreenwoodSchrodinger, 120 West 45th Street, New York, NY 10036, USA.
Sathesh BhatSchrodinger, 120 West 45th Street, New York, NY 10036, USA.
Geraldine HarrimanNimbus Therapeutics, 30 Prospect Street, Cambridge, MA 02139, USA.
Wenyan MiaoNimbus Therapeutics, 30 Prospect Street, Cambridge, MA 02139, USA.
Jennifer L RocnikNimbus Therapeutics, 30 Prospect Street, Cambridge, MA 02139, USA.
William F WestlinNimbus Therapeutics, 30 Prospect Street, Cambridge, MA 02139, USA.
Paola MutiDepartment of Oncology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4L8, Canada.
Theodoros TsakiridisDepartment of Oncology, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4L8, Canada.
H James HarwoodNimbus Therapeutics, 30 Prospect Street, Cambridge, MA 02139, USA.
Rosana KapellerNimbus Therapeutics, 30 Prospect Street, Cambridge, MA 02139, USA.
Yujin HoshidaLiver Tumor Translational Research Program, Harold C. Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Kenneth K TanabeDivison of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
Gregory R SteinbergDepartment of Medicine, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4L8, Canada. Electronic address: gsteinberg@mcmaster.ca.
Bryan C FuchsDivison of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. Electronic address: bfuchs@mgh.harvard.edu.
McMaster University · CAGilead Sciences (United States) · USHarvard University · USMassachusetts General Hospital · USSchrodinger (United States) · USThe University of Texas Southwestern Medical Center · USBoston University · USUniversity of Guelph · CA

Funding

Training Program in Cancer Biology and TherapeuticsT32CA071345 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel A. Haber, Lecia V. Sequist · 1997 to 2026
$10.6M
Molecular Prognostic Indicators in Liver Cirrhosis and CancerR01DK099558 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HOSHIDA, YUJIN · 2013 to 2016
$2.6M
The Role of EGF in Human Hepatocellular TransformationK01CA140861 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI FUCHS, BRYAN CHRISTOPHER · 2009 to 2013
$710k
CIHR 125980-1CIHR 144625-1European Research Council 671231NCI NIH HHS K01 CA140861NCI NIH HHS T32 CA071345NIDDK NIH HHS R01 DK099558
6 · The paper itself

Abstract

The incidence of hepatocellular carcinoma (HCC) is rapidly increasing due to the prevalence of obesity and non-alcoholic fatty liver disease, but the molecular triggers that initiate disease development are not fully understood. We demonstrate that mice with targeted loss-of-function point mutations within the AMP-activated protein kinase (AMPK) phosphorylation sites on acetyl-CoA carboxylase 1 (ACC1 Ser79Ala) and ACC2 (ACC2 Ser212Ala) have increased liver de novo lipogenesis (DNL) and liver lesions. The same mutation in ACC1 also increases DNL and proliferation in human liver cancer cells. Consistent with these findings, a novel, liver-specific ACC inhibitor (ND-654) that mimics the effects of ACC phosphorylation inhibits hepatic DNL and the development of HCC, improving survival of tumor-bearing rats when used alone and in combination with the multi-kinase inhibitor sorafenib. These studies highlight the importance of DNL and dysregulation of AMPK-mediated ACC phosphorylation in accelerating HCC and the potential of ACC inhibitors for treatment.

Indexed as

Acetyl-CoA CarboxylaseLipogenesisAnimalsCarcinoma, HepatocellularHep G2 CellsHumansLiver NeoplasmsMaleMicePhosphorylationRatsRats, WistarACACA protein, humanAcacb protein, mouseACC1 protein, mouseAcetyl-CoA Carboxylasecancer metabolismfibrosisfructoseinflammationmalonyl-CoANAFLDNASHnon-alcoholic fatty liver diseasenon-alcoholic steatohepatitis

Identifiers

PMID30244972
PMCPMC6643297
OpenAlexW2890605550

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.