Evidence map›Paper›PMID 33903236›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

Aberrant epithelial polarity cues drive the development of precancerous airway lesions.

Andrew Tilston-Lunel, Sarah Mazzilli, Nathan M Kingston, Aleksander D Szymaniak, Julia Hicks-Berthet, Joseph G Kern, Kristine Abo, Mary E Reid, Catalina Perdomo, Andrew A Wilson and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. 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
1.4field-weighted citation impact, top 21% 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, 20 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Signaling pathways and targeted interventions for precancers.Signal transduction and targeted therapy · 2026
    Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. AKT Phosphorylates FAM13A and Promotes Its Degradation via CUL4A/DDB1/DCAF1 E3 Complex.American journal of respiratory cell and molecular biology · 2023
    Article
  12. Review
  13. Review
  14. Emerging Cnidarian Models for the Study of Epithelial Polarity.Frontiers in cell and developmental biology · 2022
    Review
  15. Article
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

13 authors at 2 institutions in 1 country.

Andrew Tilston-LunelDepartment of Biochemistry, Boston University School of Medicine, Boston, MA 02118.
Sarah MazzilliDepartment of Medicine, Boston University School of Medicine, Boston, MA 02118.
Nathan M KingstonDepartment of Biochemistry, Boston University School of Medicine, Boston, MA 02118.
Aleksander D SzymaniakDepartment of Biochemistry, Boston University School of Medicine, Boston, MA 02118.
Julia Hicks-BerthetDepartment of Biochemistry, Boston University School of Medicine, Boston, MA 02118.ORCID 0000-0002-6549-8116
Joseph G KernDepartment of Biochemistry, Boston University School of Medicine, Boston, MA 02118.
Kristine AboDepartment of Medicine, Boston University School of Medicine, Boston, MA 02118.
Mary E ReidDepartment of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203.
Catalina PerdomoDepartment of Medicine, Boston University School of Medicine, Boston, MA 02118.
Andrew A WilsonDepartment of Medicine, Boston University School of Medicine, Boston, MA 02118.
Avrum SpiraDepartment of Medicine, Boston University School of Medicine, Boston, MA 02118.
Jennifer BeaneDepartment of Medicine, Boston University School of Medicine, Boston, MA 02118.
Xaralabos VarelasDepartment of Biochemistry, Boston University School of Medicine, Boston, MA 02118; xvarelas@bu.edu.ORCID 0000-0002-2882-4541
Boston University · USRoswell Park Comprehensive Cancer Center · US

Funding

Project-005UL1TR001430 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BAIR-MERRITT, MEGAN H, CENTER, DAVID M. · 2015 to 2024
$52.3M
BIOLOGY OF THE LUNG--MULTIDISCIPLINARY PROGRAMT32HL007035 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Darrell N. Kotton, JOSEPH P MIZGERD · 1985 to 2026
$24.3M
Multidisciplinary Training Program in Cardiovascular EpidemiologyT32HL125232 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Matthew G. Nayor, Vanessa Xanthakis · 2016 to 2026
$5.0M
Defining epithelial polarity cues that direct cell fateR01HL124392 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI VARELAS, XARALABOS · 2014 to 2024
$4.5M
Determining the roles of the Hippo pathway kinases LATS1 and LATS2 in mammary gland homeostasis and diseaseF31CA232683 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KERN, JOSEPH · 2018 to 2021
$181k
Pluripotent stem cell-based modeling of cigarette smoke injuryF30HL147426 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI ABO, KRISTINE · 2020 to 2023
$160k
Roles for YAP in multiciliogenesisF31HL132506 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BERTHET, JULIA · 2016 to 2019
$138k
YAP/TAZ-NRG1 crosstalk in airway epithelial cell fate controlF31HL146163 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI KINGSTON, NATHAN · 2019 to 2020
$91k
NCATS NIH HHS UL1 TR001430NCI NIH HHS F31 CA232683NHLBI NIH HHS F30 HL147426NHLBI NIH HHS F31 HL132506NHLBI NIH HHS F31 HL146163NHLBI NIH HHS R01 HL124392NHLBI NIH HHS T32 HL007035NHLBI NIH HHS T32 HL125232
6 · The paper itself

Abstract

Molecular events that drive the development of precancerous lesions in the bronchial epithelium, which are precursors of lung squamous cell carcinoma (LUSC), are poorly understood. We demonstrate that disruption of epithelial cellular polarity, via the conditional deletion of the apical determinant Crumbs3 (Crb3), initiates and sustains precancerous airway pathology. The loss of Crb3 in adult luminal airway epithelium promotes the uncontrolled activation of the transcriptional regulators YAP and TAZ, which stimulate intrinsic signals that promote epithelial cell plasticity and paracrine signals that induce basal-like cell growth. We show that aberrant polarity and YAP/TAZ-regulated gene expression associates with human bronchial precancer pathology and disease progression. Analyses of YAP/TAZ-regulated genes further identified the ERBB receptor ligand Neuregulin-1 (NRG1) as a key transcriptional target and therapeutic targeting of ERBB receptors as a means of preventing and treating precancerous cell growth. Our observations offer important molecular insight into the etiology of LUSC and provides directions for potential interception strategies of lung cancer.

Indexed as

Carcinoma, Squamous CellCell PolarityEpithelial CellsEpitheliumErbB ReceptorsGene Expression Regulation, NeoplasticHumansLung NeoplasmsMembrane GlycoproteinsNeuregulin-1Precancerous ConditionsSignal TransductionTranscriptional Coactivator with PDZ-Binding Motif ProteinsYAP-Signaling ProteinsCrb3 protein, mouseErbB ReceptorsMembrane GlycoproteinsNeuregulin-1Transcriptional Coactivator with PDZ-Binding Motif ProteinsYAP-Signaling Proteinsepithelial polaritylung basal cellslung precancerYAP/TAZ

Identifiers

PMID33903236
PMCPMC8106308
OpenAlexW3157688344

What OpenQuestion holds

Textmetadata
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.