Evidence map›Paper›PMID 33219129›Full record

ArticleThe Journal of biological chemistry

ABHD5 suppresses cancer cell anabolism through lipolysis-dependent activation of the AMPK/mTORC1 pathway.

Guohua Chen, Guoli Zhou, Aaron Lotvola, James G Granneman, Jian Wang

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

15 citing papers in PubMed, 25 citations in OpenAlex.

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  13. The AMPK pathway in fatty liver disease.Frontiers in physiology · 2022
    Review
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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

5 authors at 2 institutions in 1 country.

Guohua ChenDepartment of Pathology, Wayne State University School of Medicine, Detroit, Michigan, USA.
Guoli ZhouBiomedical Research Informatics Core, Clinical and Translational Sciences Institute, Michigan State University, East Lansing, Michigan, USA.
Aaron LotvolaDepartment of Oncology, Wayne State University School of Medicine, Detroit, Michigan, USA.
James G GrannemanCenter for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, Michigan, USA.
Jian WangDepartment of Pathology, Wayne State University School of Medicine, Detroit, Michigan, USA. Electronic address: jianwang@med.wayne.edu.
Wayne State University · USMichigan State University · US

Funding

Regional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DAVID P OLSON · 2013 to 2026
$24.3M
Analysis of Lipolytic Trafficking in Adipocytes.R01DK076629 · NIDDK · WAYNE STATE UNIVERSITY · PI James G Granneman, Christopher V Kelly · 2009 to 2026
$7.1M
TRAINING PROGRAM IN THE BIOLOGY OF CANCERT32CA009531 · NCI · WAYNE STATE UNIVERSITY · PI Larry H Matherly · 1985 to 2026
$5.3M
NCI NIH HHS T32 CA009531NIDDK NIH HHS P30 DK020572
6 · The paper itself

Abstract

ABHD5 is an essential coactivator of ATGL, the rate-limiting triglyceride (TG) lipase in many cell types. Importantly, ABHD5 also functions as a tumor suppressor, and ABHD5 mRNA expression levels correlate with patient survival for several cancers. Nevertheless, the mechanisms involved in ABHD5-dependent tumor suppression are not known. We found that overexpression of ABHD5 induces cell cycle arrest at the G1 phase and causes growth retardation in a panel of prostate cancer cells. Transcriptomic profiling and biochemical analysis revealed that genetic or pharmacological activation of lipolysis by ABHD5 potently inhibits mTORC1 signaling, leading to a significant downregulation of protein synthesis. Mechanistically, we found that ABHD5 elevates intracellular AMP content, which activates AMPK, leading to inhibition of mTORC1. Interestingly, ABHD5-dependent suppression of mTORC1 was abrogated by pharmacological inhibition of DGAT1 or DGAT2, isoenzymes that re-esterify fatty acids in a process that consumes ATP. Collectively, this study maps out a novel molecular pathway crucial for limiting cancer cell proliferation, in which ABHD5-mediated lipolysis creates an energy-consuming futile cycle between TG hydrolysis and resynthesis, leading to inhibition of mTORC1 and cancer cell growth arrest.

Indexed as

1-Acylglycerol-3-Phosphate O-AcyltransferaseAdenosine MonophosphateAdenosine TriphosphateAMP-Activated Protein KinasesBlotting, WesternCell CycleCell ProliferationHumansLipolysisMechanistic Target of Rapamycin Complex 1MetabolismRNA-Seq1-Acylglycerol-3-Phosphate O-AcyltransferaseABHD5 protein, humanAdenosine MonophosphateAdenosine TriphosphateAMP-Activated Protein KinasesMechanistic Target of Rapamycin Complex 1AMP-activated protein kinase (AMPK)cancer metabolismlipolysismTORαβ hydrolase domain containing 5 (ABHD5)

Identifiers

PMID33219129
PMCPMC7949079
OpenAlexW3106118460

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.