Identification of Endoglin as an epigenetically regulated tumour-suppressor gene in lung cancer

British Journal of Cancer
K O'LearyP Schmid

Abstract

The transforming growth factor-beta (TGF- β) pathway has been implicated in proliferation, migration and invasion of various cancers. Endoglin is a TGF-β accessory receptor that modulates signalling. We identified Endoglin as an epigenetically silenced tumour-suppressor gene in lung cancer by means of a genome-wide screening approach, then sought to characterise its effect on lung cancer progression. Methylation microarray and RNA sequencing were carried out on lung cancer cell lines. Epigenetic silencing of Endoglin was confirmed by methylation and expression analyses. An expression vector and a 20-gene expression panel were used to evaluate Endoglin function. Pyrosequencing was carried out on two independent cohorts comprising 112 and 202 NSCLC cases, respectively, and the impact of Endoglin methylation on overall survival (OS) was evaluated. Methylation in the promoter region resulted in silencing of Endoglin, which could be reactivated by demethylation. Increased invasion coupled with altered EMT marker expression was observed in cell lines with an epithelial-like, but not those with a mesenchymal-like, profile when Endoglin was absent. Methylation was associated with decreased OS in stage I but not in stages II-III disease...Continue Reading

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Citations

Sep 3, 2016·Seminars in Cancer Biology·Gaia CantelliVictoria Sanz-Moreno
Jan 21, 2017·Journal of Clinical Medicine·Takehiko Yokobori, Masahiko Nishiyama
Apr 30, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Hongyu TianGerard C Blobe
Dec 9, 2020·International Journal of Molecular Sciences·Steffen K Meurer, Ralf Weiskirchen
Nov 14, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Pilar Puerto-CamachoEnrique de Álava
Feb 24, 2020·Seminars in Cancer Biology·Christopher WoodmanCornelia M Wilson
Apr 4, 2021·International Journal of Molecular Sciences·Teresa González MuñozEnrique de Álava
Apr 17, 2020·Life Sciences·Sekaran SaravananVenil N Sumantran

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Datasets Mentioned

BETA
GSE36216

Methods Mentioned

BETA
RNA-seq
PCR
transfections
surgical resection
biopsies
transfection

Software Mentioned

GSNAP
Cluster
ImageJ
SPSS Statistics
GraphPad Prism
Excel
R Bioconductor Shortread package
Treeview

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