Evidence map›Paper›PMID 33503403›Full record

ArticleCell chemical biology2021

Small-molecule probe reveals a kinase cascade that links stress signaling to TCF/LEF and Wnt responsiveness.

Jiongjia Cheng, Masanao Tsuda, Karl Okolotowicz, Mary Dwyer, Paul J Bushway, Alexandre R Colas, Joseph J Lancman, Dennis Schade, Isaac Perea-Gil, Arne A N Bruyneel and 11 more

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

Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 42% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 6 institutions in 2 countries.

Jiongjia ChengHuman BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.
Masanao TsudaSanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Karl OkolotowiczHuman BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.
Mary DwyerHuman BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.
Paul J BushwaySanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; University of California, San Diego, San Diego, CA 92093, USA.
Alexandre R ColasSanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Joseph J LancmanSanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Dennis SchadeHuman BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA; Institute of Pharmacy, Christian-Albrechts-University of Kiel, Gutenbergstrasse 76, Kiel, Germany.
Isaac Perea-GilCardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.
Arne A N BruyneelCardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.
Jaechol LeeCardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.
Nirmal VadgamaCardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.
Justine QuachHuman BioMolecular Research Institute, 5310 Eastgate Mall, San Diego, CA 92121, USA.
Wesley L McKeithanSanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Cardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.
Travis L BiecheleDepartment of Pharmacology, University of Washington, Seattle, WA 98105, USA.
Joseph C WuCardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA; Department of Medicine, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.
Randall T MoonDepartment of Pharmacology, University of Washington, Seattle, WA 98105, USA.
P Duc Si DongSanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Ioannis KarakikesCardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA; Department of Cardiothoracic Surgery, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA.
John R CashmanSanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Mark MercolaSanford-Burnham-Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; University of California, San Diego, San Diego, CA 92093, USA; Cardiovascular Institute, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA; Department of Medicine, Stanford University, 240 Pasteur Drive, Palo Alto, CA 94305, USA. Electronic address: mmercola@stanford.edu.
Sanford Burnham Prebys Medical Discovery Institute · USCardiovascular Institute of the South · USHuman BioMolecular Research Institute · USPalo Alto University · USUniversity of Washington · USChristian-Albrechts-Universität zu Kiel · DE

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI ELENA B PASQUALE · 1985 to 2026
$107.2M
Project 3 (Mercola)P01HL141084 · NHLBI · STANFORD UNIVERSITY · PI Joseph C. Wu · 2019 to 2026
$21.1M
Genome Editing of Human iPSCs to Study Inherited Hypertrophic CardiomyopathyR01HL126527 · NHLBI · STANFORD UNIVERSITY · PI QI, LEI STANLEY, WU, JOSEPH C. · 2015 to 2022
$5.4M
Human iPSC Model to Elucidate Metabolic Interplay in Diabetic CardimyopathyR01HL146690 · NHLBI · STANFORD UNIVERSITY · PI LIAO, RONGLIH, MERCOLA, MARK · 2019 to 2025
$5.1M
Functional Analysis of T2D Associated Non-coding SNPsU01DK105541 · NIDDK · LUDWIG INSTITUTE FOR CANCER RES LTD · PI FRAZER, KELLY A, REN, BING · 2015 to 2019
$4.6M
MicroRNA Control of Dilated CardiomyopathyR01HL130840 · NHLBI · STANFORD UNIVERSITY · PI MARK MERCOLA, Shankar Subramaniam · 2016 to 2026
$4.6M
Unraveling the pathogenesis of familial dilated cardiomyopathy towards precision medicineR01HL139679 · NHLBI · STANFORD UNIVERSITY · PI Ioannis Karakikes · 2018 to 2026
$4.2M
Unlocking Regenerative Potential through in Vivo Genetic ReprogrammingDP2DK098092 · NIDDK · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI DONG, P. DUC SI · 2012 to 2012
$2.9M
microRNAs and Integrative Control on Cardiopoiesis - CHANGE OF GRANTEE INSTITUTIOR01HL113601 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MERCOLA, MARK · 2012 to 2016
$2.2M
Discovery of Small Molecule Promoters of Cardiomyocyte Proliferation to Restore Cardiac Performance in DiseaseR01HL148827 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI COLAS, ALEXANDRE ROMAIN · 2019 to 2022
$2.0M
Discovery of small molecule regulators of atrial cardiomyocyte action potential duration to restore normal cardiac rhythm in atrial fibrillationR01HL153645 · NHLBI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI COLAS, ALEXANDRE ROMAIN · 2021 to 2024
$1.9M
Small Molecule NOTCH Inhibitors for the treatment of pulmonary hypertensionR01HL132225 · NHLBI · STANFORD UNIVERSITY · PI MERCOLA, MARK, THISTLETHWAITE, PATRICIA A · 2016 to 2019
$1.7M
NCI NIH HHS P30 CA030199NCI NIH HHS R41 CA176931NCI NIH HHS R43 CA203566NHLBI NIH HHS P01 HL141084NHLBI NIH HHS R00 HL104002NHLBI NIH HHS R01 HL113601NHLBI NIH HHS R01 HL126527NHLBI NIH HHS R01 HL130840NHLBI NIH HHS R01 HL132225NHLBI NIH HHS R01 HL139679NHLBI NIH HHS R01 HL146690NHLBI NIH HHS R01 HL148827NHLBI NIH HHS R01 HL153645NHLBI NIH HHS R37 HL059502NIDDK NIH HHS DP2 DK098092NIDDK NIH HHS U01 DK105541
6 · The paper itself

Abstract

Wnt signaling plays a central role in tissue maintenance and cancer. Wnt activates downstream genes through β-catenin, which interacts with TCF/LEF transcription factors. A major question is how this signaling is coordinated relative to tissue organization and renewal. We used a recently described class of small molecules that binds tubulin to reveal a molecular cascade linking stress signaling through ATM, HIPK2, and p53 to the regulation of TCF/LEF transcriptional activity. These data suggest a mechanism by which mitotic and genotoxic stress can indirectly modulate Wnt responsiveness to exert coherent control over cell shape and renewal. These findings have implications for understanding tissue morphogenesis and small-molecule anticancer therapeutics.

Indexed as

Animalsbeta CateninCells, CulturedHumansMaleMolecular ProbesProtein Serine-Threonine KinasesSmall Molecule LibrariesTCF Transcription FactorsWnt Signaling PathwayXenopusZebrafishbeta CateninMolecular ProbesProtein Serine-Threonine KinasesSmall Molecule LibrariesTCF Transcription Factorsataxia telangiectasia mutated/ATMAurora kinaseshomeodomain-interacting protein kinase/HIPK2LEFp53TCFWntβ-catenin

Identifiers

PMID33503403
PMCPMC8140986
OpenAlexW3122156624

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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.