Evidence map›Paper›PMID 27633013›Full record

ArticleGenes & development2016

Genetic ablation of Smoothened in pancreatic fibroblasts increases acinar-ductal metaplasia.

Xin Liu, Jason R Pitarresi, Maria C Cuitiño, Raleigh D Kladney, Sarah A Woelke, Gina M Sizemore, Sunayana G Nayak, Onur Egriboz, Patrick G Schweickert, Lianbo Yu and 14 more

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

Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
–field-weighted citation impact
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

34 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Article
  3. Cellular Origins and Lineage Plasticity in Cancer.Cold Spring Harbor perspectives in medicine · 2024
    Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. The Role of Smoothened in Cancer.International journal of molecular sciences · 2020
    Review
  18. Review
  19. Review
  20. PTEN in the Stroma.Cold Spring Harbor perspectives in medicine · 2019
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 2 institutions in 1 country.

Xin LiuComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Jason R PitarresiComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Maria C CuitiñoComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Raleigh D KladneyComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Sarah A WoelkeComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA;
Gina M SizemoreComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Sunayana G NayakComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Onur EgribozComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Patrick G SchweickertDepartment of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA; the Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, USA; the Bindley Bioscience Center, Purdue University, West Lafayette, Indiana 47907, USA;
Lianbo YuDepartment of Biomedical Informatics' Center for Biostatistics, The Ohio State University, Columbus, Ohio 43210, USA.
Stefan TrelaComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Daniel J SchillingComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Shannon K HalloranComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Maokun LiComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Shourik DuttaComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Soledad A FernandezDepartment of Biomedical Informatics' Center for Biostatistics, The Ohio State University, Columbus, Ohio 43210, USA.
Thomas J RosolComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Veterinary Biosciences, The Ohio State University, Columbus, Ohio 43210, USA.
Gregory B LesinskiComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Reena ShakyaComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA;
Thomas LudwigComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Stephen F KoniecznyDepartment of Biological Sciences, Purdue University, West Lafayette, Indiana 47907, USA; the Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, USA; the Bindley Bioscience Center, Purdue University, West Lafayette, Indiana 47907, USA;
Gustavo LeoneComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Jinghai WuComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
Michael C OstrowskiComprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, USA; Cancer Biology and Genetics Department, The Ohio State University, Columbus, Ohio 43210, USA;
The Ohio State University · USCenter for Cancer Research · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
Suppression of Mammary Tumorigenesis by Stromal p53P01CA097189 · NCI · OHIO STATE UNIVERSITY · PI ROSOL, THOMAS J · 2004 to 2016
$16.1M
Tumor Suppressor Roles of E2F7 & E2F8 in Hepatocellular Carcinoma (HCC)R01CA121275 · NCI · OHIO STATE UNIVERSITY · PI LEONE, GUSTAVO WALTER · 2008 to 2018
$3.1M
Kras-Induced Cellular Plasticity in Pancreatic CancerR01CA124586 · NCI · PURDUE UNIVERSITY · PI KONIECZNY, STEPHEN F · 2008 to 2017
$3.1M
The Role of Cancer Associated Fibroblasts in Pancreatic Tumor ProgressionF31CA189757 · NCI · OHIO STATE UNIVERSITY · PI PITARRESI, JASON R. · 2015 to 2015
$36k
NCI NIH HHS F31 CA189757NCI NIH HHS P01 CA097189NCI NIH HHS P30 CA016058NCI NIH HHS R01 CA121275NCI NIH HHS R01 CA124586
6 · The paper itself

Abstract

The contribution of the microenvironment to pancreatic acinar-to-ductal metaplasia (ADM), a preneoplastic transition in oncogenic Kras-driven pancreatic cancer progression, is currently unclear. Here we show that disruption of paracrine Hedgehog signaling via genetic ablation of Smoothened (Smo) in stromal fibroblasts in a Kras(G12D) mouse model increased ADM. Smo-deleted fibroblasts had higher expression of transforming growth factor-α (Tgfa) mRNA and secreted higher levels of TGFα, leading to activation of EGFR signaling in acinar cells and increased ADM. The mechanism involved activation of AKT and noncanonical activation of the GLI family transcription factor GLI2. GLI2 was phosphorylated at Ser230 in an AKT-dependent fashion and directly regulated Tgfa expression in fibroblasts lacking Smo Additionally, Smo-deleted fibroblasts stimulated the growth of Kras(G12D)/Tp53(R172H) pancreatic tumor cells in vivo and in vitro. These results define a non-cell-autonomous mechanism modulating Kras(G12D)-driven ADM that is balanced by cross-talk between Hedgehog/SMO and AKT/GLI2 pathways in stromal fibroblasts.

Indexed as

Carcinoma, Pancreatic DuctalAnimalsCell ProliferationCells, CulturedEpithelial CellsErbB ReceptorsFibroblastsGene DeletionKruppel-Like Transcription FactorsMetaplasiaMiceMice, Inbred C57BLPancreasPancreatic NeoplasmsSignal TransductionSmoothened ReceptorEGFR protein, mouseErbB ReceptorsGli2 protein, mouseKruppel-Like Transcription FactorsSmoothened ReceptorSmo protein, mouseTransforming Growth Factor alphaZinc Finger Protein Gli2acinar-to-ductal metaplasiaAKT signalingEGFR signalinghedgehog signalingstromal fibroblast

Identifiers

PMID27633013
PMCPMC5066238
OpenAlexW2519938316

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Registered trials

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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.