Evidence map›Paper›PMID 31355336›Full record

ArticleScience advances2019

The CREB coactivator CRTC2 promotes oncogenesis in LKB1-mutant non-small cell lung cancer.

Laura Rodón, Robert U Svensson, Ezra Wiater, Matthew G H Chun, Wen-Wei Tsai, Lillian J Eichner, Reuben J Shaw, Marc Montminy

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 10% 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

28 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Targeting CRTC2 reversesProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  7. Review
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  12. Review
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  18. Aging, adaptation and maladaptation.Frontiers in aging · 2023
    Article
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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

8 authors at 1 institution in 1 country.

Laura RodónPeptide Biology Laboratories, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.ORCID 0000-0001-5498-3389
Robert U SvenssonDepartment of Molecular and Cell Biology, Salk Institute for Biological Studies, La Jolla, CA 92037 USA.
Ezra WiaterPeptide Biology Laboratories, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Matthew G H ChunDepartment of Molecular and Cell Biology, Salk Institute for Biological Studies, La Jolla, CA 92037 USA.
Wen-Wei TsaiPeptide Biology Laboratories, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Lillian J EichnerDepartment of Molecular and Cell Biology, Salk Institute for Biological Studies, La Jolla, CA 92037 USA.
Reuben J ShawDepartment of Molecular and Cell Biology, Salk Institute for Biological Studies, La Jolla, CA 92037 USA.ORCID 0000-0002-1555-8977
Marc MontminyPeptide Biology Laboratories, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.ORCID 0000-0001-8118-6174
Salk Institute for Biological Studies · US

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Reuben Shaw · 1985 to 2026
$82.8M
Tuberous Sclerosis-Pathway and PathogenesisP01CA120964 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI David J. Kwiatkowski · 2007 to 2026
$35.9M
Decoding And Targeting The LKB1-AMPK Signaling Pathway In CancerR35CA220538 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Reuben Shaw · 2017 to 2026
$11.3M
Regulation of Hepatic Gluconeogenesis by the CREB:TORC2 PathwayR01DK083834 · NIDDK · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI MONTMINY, MARC R · 2009 to 2022
$3.7M
NCI NIH HHS P01 CA120964NCI NIH HHS P30 CA014195NCI NIH HHS R35 CA220538NIDDK NIH HHS R01 DK083834
6 · The paper itself

Abstract

The LKB1 tumor suppressor is often mutationally inactivated in non-small cell lung cancer (NSCLC). LKB1 phosphorylates and activates members of the AMPK family of Ser/Thr kinases. Within this family, the salt-inducible kinases (SIKs) modulate gene expression in part via the inhibitory phosphorylation of the CRTCs, coactivators for CREB (cAMP response element-binding protein). The loss of LKB1 causes SIK inactivation and the induction of the CRTCs, leading to the up-regulation of CREB target genes. We identified CRTC2 as a critical factor in LKB1-deficient NSCLC. CRTC2 is unphosphorylated and therefore constitutively activated in LKB1-mutant NSCLC, where it promotes tumor growth, in part via the induction of the inhibitor of DNA binding 1 (ID1), a bona fide CREB target gene. As ID1 expression is up-regulated and confers poor prognosis in LKB1-deficient NSCLC, our results suggest that small molecules that inhibit CRTC2 and ID1 activity may provide therapeutic benefit to individuals with NSCLC.

Indexed as

Adenocarcinoma of LungAMP-Activated Protein Kinase KinasesAnimalsCarcinogenesisCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationCyclic AMP Response Element-Binding ProteinFemaleGene Expression Regulation, NeoplasticHumansInhibitor of Differentiation Protein 1Lung NeoplasmsMice, SCIDMutationPrognosisAMP-Activated Protein Kinase KinasesCRTC2 protein, humanCyclic AMP Response Element-Binding ProteinID1 protein, humanInhibitor of Differentiation Protein 1Protein Serine-Threonine KinasesSTK11 protein, humanTranscription Factors

Identifiers

PMID31355336
PMCPMC6656544
OpenAlexW2963425570

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.