Evidence map›Paper›PMID 26483386›Full record

ArticleJournal of cell science2015

Carcinoma cells induce lumen filling and EMT in epithelial cells through soluble E-cadherin-mediated activation of EGFR.

Pratima U Patil, Julia D'Ambrosio, Landon J Inge, Robert W Mason, Ayyappan K Rajasekaran

Open access · bronzeAbstract read
In one paragraph

Article in Journal of cell science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

24 citing papers in PubMed, 39 citations in OpenAlex.

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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

5 authors at 4 institutions in 1 country.

Pratima U PatilDepartment of Biological Sciences, University of Delaware, Newark, DE 19716, USA Nemours Center for Childhood Cancer Research, Department of Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA.
Julia D'AmbrosioNemours Center for Childhood Cancer Research, Department of Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA.
Landon J IngeThoracic and Esophageal disease, Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Robert W MasonNemours Center for Childhood Cancer Research, Department of Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE 19803, USA.
Ayyappan K RajasekaranDepartment of Biological Sciences, University of Delaware, Newark, DE 19716, USA Therapy Architects, LLC, 2700, Silverside Road, Wilmington, DE 19810, USA raj@therapyarchitects.com.
Alfred I. duPont Hospital for Children · USCommunity Health Systems - Dupont Hospital · USSt. Joseph's Hospital and Medical Center · USUniversity of Delaware · US

Funding

Center for Pediatric ResearchP20GM103464 · NIGMS · NEMOURS CHILDREN'S HOSPITAL, DELAWARE · PI SHAFFER, THOMAS H · 2012 to 2014
$5.6M
Center for Pediatric Research Pilot ProgramP30GM114736 · NIGMS · NEMOURS CHILDREN'S HOSPITAL, DELAWARE · PI SHAFFER, THOMAS H · 2015 to 2019
$5.1M
Role of Beta Subunit of Sodium Pump in Cell AdhesionR01DK056216 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RAJASEKARAN, AYYAPPAN K. · 2001 to 2009
$2.1M
NIDDK NIH HHS DK56216NIDDK NIH HHS R01 DK056216NIGMS NIH HHS P20 GM103464NIGMS NIH HHS P20GM103464NIGMS NIH HHS P30 GM114736
6 · The paper itself

Abstract

In epithelial cancers, carcinoma cells coexist with normal cells. Although it is known that the tumor microenvironment (TME) plays a pivotal role in cancer progression, it is not completely understood how the tumor influences adjacent normal epithelial cells. In this study, a three-dimensional co-culture system comprising non-transformed epithelial cells (MDCK) and transformed carcinoma cells (MSV-MDCK) was used to demonstrate that carcinoma cells sequentially induce preneoplastic lumen filling and epithelial-mesenchymal transition (EMT) in epithelial cysts. MMP-9 secreted by carcinoma cells cleaves cellular E-cadherin (encoded by CDH1) from epithelial cells to generate soluble E-cadherin (sE-cad), a pro-oncogenic protein. We show that sE-cad induces EGFR activation, resulting in lumen filling in MDCK cysts. Long-term sE-cad treatment induced EMT. sE-cad caused lumen filling by induction of the ERK signaling pathway and triggered EMT through the sustained activation of the AKT pathway. Although it is known that sE-cad induces MMP-9 release and consequent EGFR activation in tumor cells, our results, for the first time, demonstrate that carcinoma cells can induce sE-cad shedding in adjacent epithelial cells, which leads to EGFR activation and the eventual transdifferentiation of the normal epithelial cells.

Indexed as

Epithelial-Mesenchymal TransitionAnimalsCadherinsCarcinomaDogsEpithelial CellsErbB ReceptorsMadin Darby Canine Kidney CellsMatrix Metalloproteinase 9Proto-Oncogene Proteins c-aktCadherinsErbB ReceptorsMatrix Metalloproteinase 9Proto-Oncogene Proteins c-aktEGFRMMP-9Soluble E-cadherinTransdifferentiation

Identifiers

PMID26483386
PMCPMC4712814
OpenAlexW2187793946

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.