Global evaluation of Eph receptors and ephrins in lung adenocarcinomas identifies EphA4 as an inhibitor of cell migration and invasion

Pierre Saintigny, Shaohua Peng, Li Zhang, Banibrata Sen, Ignacio I. Wistuba, Scott M. Lippman, Luc Girard, John D. Minna, John V. Heymach, Faye M. Johnson

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The Eph family of receptors is the largest family of receptor tyrosine kinases, but it remains poorly studied in lung cancer. We aimed to systematically explore the human Eph receptors and their ligands, the ephrins, in lung adenocarcinoma. The prognostic impact of Eph receptor and ephrin gene expression was analyzed using 2 independent cohorts of lung adenocarcinoma. Gene expression profiles in lung adenocarcinoma compared with normal adjacent lung were studied in 3 independent cohorts and in cell lines. Gene expression profiles were validated with quantitative polymerase chain reaction (qPCR) and Western blotting in cell lines. Functional studies to assess the role of Eph receptor A4 (EphA4) were carried out in vitro. The biological effects of EphA4 in lung cancer cell lines were assayed following overexpression and knockdown. Of the 11 Eph receptors and 8 ephrins analyzed, only EphA4 and ephrin A1 gene expression were consistently associated with an improved outcome in patients with lung adenocarcinoma. Expression levels of EphA4 by microarray correlated well with expression levels measured by qPCR and Western blotting. EphA4 overexpression reduced cell migration and invasion but did not affect cell cycle, apoptosis, or drug sensitivity. Surprisingly, EphA4 was expressed at higher levels in cancer compared with noncancer tissues and cell lines. EphA4 gene expression is associated with an improved outcome in patients with resected lung adenocarcinoma, possibly by affecting cancer cell migration and invasion.

Original languageEnglish (US)
Pages (from-to)2021-2032
Number of pages12
JournalMolecular Cancer Therapeutics
Volume11
Issue number9
DOIs
StatePublished - Sep 2012

Fingerprint

EphA1 Receptor
Eph Family Receptors
Ephrins
Cell Movement
Cell Line
Transcriptome
Gene Expression
Ephrin-A1
Lung Neoplasms
Western Blotting
Polymerase Chain Reaction
Adenocarcinoma of lung
Receptor Protein-Tyrosine Kinases
Neoplasms
Cell Cycle
Apoptosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Global evaluation of Eph receptors and ephrins in lung adenocarcinomas identifies EphA4 as an inhibitor of cell migration and invasion. / Saintigny, Pierre; Peng, Shaohua; Zhang, Li; Sen, Banibrata; Wistuba, Ignacio I.; Lippman, Scott M.; Girard, Luc; Minna, John D.; Heymach, John V.; Johnson, Faye M.

In: Molecular Cancer Therapeutics, Vol. 11, No. 9, 09.2012, p. 2021-2032.

Research output: Contribution to journalArticle

Saintigny, Pierre ; Peng, Shaohua ; Zhang, Li ; Sen, Banibrata ; Wistuba, Ignacio I. ; Lippman, Scott M. ; Girard, Luc ; Minna, John D. ; Heymach, John V. ; Johnson, Faye M. / Global evaluation of Eph receptors and ephrins in lung adenocarcinomas identifies EphA4 as an inhibitor of cell migration and invasion. In: Molecular Cancer Therapeutics. 2012 ; Vol. 11, No. 9. pp. 2021-2032.
@article{de12965dd89c4129827116110b9e26f3,
title = "Global evaluation of Eph receptors and ephrins in lung adenocarcinomas identifies EphA4 as an inhibitor of cell migration and invasion",
abstract = "The Eph family of receptors is the largest family of receptor tyrosine kinases, but it remains poorly studied in lung cancer. We aimed to systematically explore the human Eph receptors and their ligands, the ephrins, in lung adenocarcinoma. The prognostic impact of Eph receptor and ephrin gene expression was analyzed using 2 independent cohorts of lung adenocarcinoma. Gene expression profiles in lung adenocarcinoma compared with normal adjacent lung were studied in 3 independent cohorts and in cell lines. Gene expression profiles were validated with quantitative polymerase chain reaction (qPCR) and Western blotting in cell lines. Functional studies to assess the role of Eph receptor A4 (EphA4) were carried out in vitro. The biological effects of EphA4 in lung cancer cell lines were assayed following overexpression and knockdown. Of the 11 Eph receptors and 8 ephrins analyzed, only EphA4 and ephrin A1 gene expression were consistently associated with an improved outcome in patients with lung adenocarcinoma. Expression levels of EphA4 by microarray correlated well with expression levels measured by qPCR and Western blotting. EphA4 overexpression reduced cell migration and invasion but did not affect cell cycle, apoptosis, or drug sensitivity. Surprisingly, EphA4 was expressed at higher levels in cancer compared with noncancer tissues and cell lines. EphA4 gene expression is associated with an improved outcome in patients with resected lung adenocarcinoma, possibly by affecting cancer cell migration and invasion.",
author = "Pierre Saintigny and Shaohua Peng and Li Zhang and Banibrata Sen and Wistuba, {Ignacio I.} and Lippman, {Scott M.} and Luc Girard and Minna, {John D.} and Heymach, {John V.} and Johnson, {Faye M.}",
year = "2012",
month = "9",
doi = "10.1158/1535-7163.MCT-12-0030",
language = "English (US)",
volume = "11",
pages = "2021--2032",
journal = "Molecular Cancer Therapeutics",
issn = "1535-7163",
publisher = "American Association for Cancer Research Inc.",
number = "9",

}

TY - JOUR

T1 - Global evaluation of Eph receptors and ephrins in lung adenocarcinomas identifies EphA4 as an inhibitor of cell migration and invasion

AU - Saintigny, Pierre

AU - Peng, Shaohua

AU - Zhang, Li

AU - Sen, Banibrata

AU - Wistuba, Ignacio I.

AU - Lippman, Scott M.

AU - Girard, Luc

AU - Minna, John D.

AU - Heymach, John V.

AU - Johnson, Faye M.

PY - 2012/9

Y1 - 2012/9

N2 - The Eph family of receptors is the largest family of receptor tyrosine kinases, but it remains poorly studied in lung cancer. We aimed to systematically explore the human Eph receptors and their ligands, the ephrins, in lung adenocarcinoma. The prognostic impact of Eph receptor and ephrin gene expression was analyzed using 2 independent cohorts of lung adenocarcinoma. Gene expression profiles in lung adenocarcinoma compared with normal adjacent lung were studied in 3 independent cohorts and in cell lines. Gene expression profiles were validated with quantitative polymerase chain reaction (qPCR) and Western blotting in cell lines. Functional studies to assess the role of Eph receptor A4 (EphA4) were carried out in vitro. The biological effects of EphA4 in lung cancer cell lines were assayed following overexpression and knockdown. Of the 11 Eph receptors and 8 ephrins analyzed, only EphA4 and ephrin A1 gene expression were consistently associated with an improved outcome in patients with lung adenocarcinoma. Expression levels of EphA4 by microarray correlated well with expression levels measured by qPCR and Western blotting. EphA4 overexpression reduced cell migration and invasion but did not affect cell cycle, apoptosis, or drug sensitivity. Surprisingly, EphA4 was expressed at higher levels in cancer compared with noncancer tissues and cell lines. EphA4 gene expression is associated with an improved outcome in patients with resected lung adenocarcinoma, possibly by affecting cancer cell migration and invasion.

AB - The Eph family of receptors is the largest family of receptor tyrosine kinases, but it remains poorly studied in lung cancer. We aimed to systematically explore the human Eph receptors and their ligands, the ephrins, in lung adenocarcinoma. The prognostic impact of Eph receptor and ephrin gene expression was analyzed using 2 independent cohorts of lung adenocarcinoma. Gene expression profiles in lung adenocarcinoma compared with normal adjacent lung were studied in 3 independent cohorts and in cell lines. Gene expression profiles were validated with quantitative polymerase chain reaction (qPCR) and Western blotting in cell lines. Functional studies to assess the role of Eph receptor A4 (EphA4) were carried out in vitro. The biological effects of EphA4 in lung cancer cell lines were assayed following overexpression and knockdown. Of the 11 Eph receptors and 8 ephrins analyzed, only EphA4 and ephrin A1 gene expression were consistently associated with an improved outcome in patients with lung adenocarcinoma. Expression levels of EphA4 by microarray correlated well with expression levels measured by qPCR and Western blotting. EphA4 overexpression reduced cell migration and invasion but did not affect cell cycle, apoptosis, or drug sensitivity. Surprisingly, EphA4 was expressed at higher levels in cancer compared with noncancer tissues and cell lines. EphA4 gene expression is associated with an improved outcome in patients with resected lung adenocarcinoma, possibly by affecting cancer cell migration and invasion.

UR - http://www.scopus.com/inward/record.url?scp=84866118854&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84866118854&partnerID=8YFLogxK

U2 - 10.1158/1535-7163.MCT-12-0030

DO - 10.1158/1535-7163.MCT-12-0030

M3 - Article

C2 - 22807579

AN - SCOPUS:84866118854

VL - 11

SP - 2021

EP - 2032

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

SN - 1535-7163

IS - 9

ER -