Evidence map›Paper›PMID 35858546›Full record

ArticleCell reports2022

PTEN and LKB1 are differentially required in Gli1-expressing mesenchymal cells to suppress gastrointestinal polyposis.

Jennifer L Cotton, Kyvan Dang, Lu Hu, Yang Sun, Alka Singh, Mihir S Rajurkar, Qi Li, Xu Wu, Junhao Mao

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

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.6field-weighted citation impact, top 36% 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

2 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. 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

9 authors at 3 institutions in 1 country.

Jennifer L CottonDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Kyvan DangDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Lu HuCutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Yang SunCutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Alka SinghDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Mihir S RajurkarDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Qi LiDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Xu WuCutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. Electronic address: xwu@cbrc2.mgh.harvard.edu.
Junhao MaoDepartment of Molecular, Cell and Cancer Biology, University of Massachusetts Chan Medical School, Worcester, MA, USA. Electronic address: junhao.mao@umassmed.edu.
University of Massachusetts Chan Medical School · USHarvard University · USMassachusetts General Hospital · US

Funding

Targeting dynamic palmitoylation of TEAD transcription factorsR01CA238270 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI MAO, JUNHAO, WU, XU · 2019 to 2023
$2.7M
Chemical approach to study autopalmitoylation of transcription factorsR01DK107651 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI LUO, XUELIAN, WU, XU · 2016 to 2020
$1.9M
Dependence for TEAD transcription factors in intestinal development and polyposisR01DK127180 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MAO, JUNHAO · 2020 to 2024
$1.9M
Mechanism of YAP/TAZ crosstalk with Wnt signalingR01DK127207 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI MAO, JUNHAO · 2021 to 2024
$1.5M
NCI NIH HHS R01 CA238270NIDDK NIH HHS R01 DK107651NIDDK NIH HHS R01 DK127180NIDDK NIH HHS R01 DK127207
6 · The paper itself

Abstract

PTEN and LKB1 are intimately associated with gastrointestinal tumorigenesis. Mutations of PTEN or LKB1 lead to Cowden syndrome and Peutz-Jeghers syndrome characterized by development of gastrointestinal polyps. However, the cells of origin of these polyps and underlying mechanism remain unclear. Here, we reveal that PTEN or LKB1 deficiency in Gli1+ gut mesenchymal cells, but not intestinal epithelium, drives polyp formation histologically resembling polyposis in human patients. Mechanistically, although PTEN and LKB1 converge to regulate mTOR/AKT signaling in various tumor contexts, we find that mTOR is essential for PTEN-deletion-induced polyp formation but is largely dispensable for polyposis induced by mesenchymal LKB1 deficiency. Altogether, our studies identify Gli1-expressing mesenchymal cells as a common cell of origin for polyposis associated with PTEN and LKB1 and reveal their engagement of different downstream pathways in gut mesenchyme to suppress gastrointestinal tumorigenesis.

Indexed as

Colorectal NeoplasmsPeutz-Jeghers SyndromeAMP-Activated Protein Kinase KinasesCell Transformation, NeoplasticHumansProtein Serine-Threonine KinasesPTEN PhosphohydrolaseTOR Serine-Threonine KinasesZinc Finger Protein GLI1AMP-Activated Protein Kinase KinasesGLI1 protein, humanProtein Serine-Threonine KinasesPTEN PhosphohydrolasePTEN protein, humanSTK11 protein, humanTOR Serine-Threonine KinasesZinc Finger Protein GLI1AKTCP: Cell biologygastrointestinal polyposisGli1intestinal mesenchymeLKB1mTORPTENtumorigenesis

Identifiers

PMID35858546
PMCPMC9764383
OpenAlexW4286250788

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.