Evidence map›Paper›PMID 29449326›Full record

ArticleEMBO molecular medicine2018

Fatty acid synthase mediates EGFR palmitoylation in EGFR mutated non-small cell lung cancer.

Azhar Ali, Elena Levantini, Jun Ting Teo, Julian Goggi, John G Clohessy, Chan Shuo Wu, Leilei Chen, Henry Yang, Indira Krishnan, Olivier Kocher and 5 more

Open access · goldAbstract read
In one paragraph

Article in EMBO molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 4% 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

126 citing papers in PubMed, 1 synthesis or guideline pooled it, 177 citations in OpenAlex.

  1. Pooled it
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  15. Crosstalk between protein lipidation and ubiquitination in tumor biology.Apoptosis : an international journal on programmed cell death · 2026
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66 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

15 authors at 4 institutions in 3 countries.

Azhar AliCancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore csiazhar@nus.edu.sg csictm@nus.edu.sg daniel.tenen@nus.edu.sg.ORCID 0000-0002-5895-9076
Elena LevantiniHarvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.
Jun Ting TeoCancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore.
Julian GoggiSingapore Bioimaging Consortium (A*STAR), Singapore City, Singapore.
John G ClohessyBeth Israel Deaconess Medical Center, Boston, MA, USA.
Chan Shuo WuCancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore.
Leilei ChenCancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore.
Henry YangCancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore.
Indira KrishnanBeth Israel Deaconess Medical Center, Boston, MA, USA.
Olivier KocherBeth Israel Deaconess Medical Center, Boston, MA, USA.
Junyan ZhangBeth Israel Deaconess Medical Center, Boston, MA, USA.
Ross A SooCancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore.
Kishore BhakooSingapore Bioimaging Consortium (A*STAR), Singapore City, Singapore.
Tan Min ChinCancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore csiazhar@nus.edu.sg csictm@nus.edu.sg daniel.tenen@nus.edu.sg.ORCID 0000-0002-3289-8498
Daniel G TenenCancer Science Institute of Singapore, National University of Singapore, Singapore City, Singapore csiazhar@nus.edu.sg csictm@nus.edu.sg daniel.tenen@nus.edu.sg.ORCID 0000-0002-6423-3888
National University of Singapore · SGBeth Israel Deaconess Medical Center · USAgency for Science, Technology and Research · SGHarvard University · US

Funding

Transcriptional and epigenetic heterogeneity of stem/progenitor cellsP01HL131477 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI DANIEL G TENEN · 2017 to 2026
$24.6M
Mechanisms of regulation by RNA in acute myeloid leukemiaR35CA197697 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI TENEN, DANIEL G · 2015 to 2021
$7.1M
NCI NIH HHS R35 CA197697NHLBI NIH HHS P01 HL131477
6 · The paper itself

Abstract

Metabolic reprogramming is widely known as a hallmark of cancer cells to allow adaptation of cells to sustain survival signals. In this report, we describe a novel oncogenic signaling pathway exclusively acting in mutated epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) with acquired tyrosine kinase inhibitor (TKI) resistance. Mutated EGFR mediates TKI resistance through regulation of the fatty acid synthase (FASN), which produces 16-C saturated fatty acid palmitate. Our work shows that the persistent signaling by mutated EGFR in TKI-resistant tumor cells relies on EGFR palmitoylation and can be targeted by Orlistat, an FDA-approved anti-obesity drug. Inhibition of FASN with Orlistat induces EGFR ubiquitination and abrogates EGFR mutant signaling, and reduces tumor growths both in culture systems and

Indexed as

LipoylationAnimalsCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationDrug Resistance, NeoplasmErbB ReceptorsFatty AcidsFatty Acid SynthasesGene Expression Regulation, NeoplasticGene SilencingLung NeoplasmsMaleMice, TransgenicModels, BiologicalMutationEGFR protein, humanErbB ReceptorsFatty AcidsFatty Acid SynthasesOrlistatProtein Kinase InhibitorsProto-Oncogene Proteins c-aktacquired resistanceEGFR‐TKIFASNNSCLCpalmitoylation

Identifiers

PMID29449326
PMCPMC5840543
OpenAlexW2788719551

What OpenQuestion 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 OpenQuestion graph.