Alternatively sliced RAGEv1 inhibits tumorigenesis through suppression of JNK signaling

Anastasia Z. Kalea, Fiona See, Evis Harja, Maria Arriero, Ann Marie Schmidt, Barry Hudson

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Receptor for advanced glycation end products (RAGE) and its ligands are overexpressed in multiple cancers. RAGE has been implicated in tumorigenesis and metastasis, but little is known of the mechanisms involved. In this study, we define a specific functional role for an alternate splice variant termed RAGE splice variant 1 (RAGEv1), which encodes a soluble endogenous form of the receptor that inhibits tumorigenesis. RAGEv1 was downregulated in lung, prostate, and brain tumors relative to control matched tissues. Overexpressing RAGEv1 in tumor cells altered RAGE ligand stimulation of several novel classes of genes that are critical in tumorigenesis and metastasis. Additionally, RAGEv1 inhibited tumor formation, cell invasion, and angiogenesis induced by RAGE ligand signaling. Analysis of signal transduction pathways underlying these effects revealed marked suppression of c-jun-NH2-kinase (JNK) pathway signaling, and JNK inhibition suppressed signaling through the RAGE pathway. Tumors expressing RAGEv1 were significantly smaller than wild-type tumors and displayed prominently reduced activation of JNK. Our results identify RAGEv1 as a novel suppressor, the study of which may offer new cancer therapeutic directions.

Original languageEnglish
Pages (from-to)5628-5638
Number of pages11
JournalCancer Research
Volume70
Issue number13
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

Fingerprint

Carcinogenesis
Phosphotransferases
Neoplasms
Ligands
Neoplasm Metastasis
Brain Neoplasms
Advanced Glycosylation End Product-Specific Receptor
Prostate
Signal Transduction
Down-Regulation
Lung
Genes
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Alternatively sliced RAGEv1 inhibits tumorigenesis through suppression of JNK signaling. / Kalea, Anastasia Z.; See, Fiona; Harja, Evis; Arriero, Maria; Schmidt, Ann Marie; Hudson, Barry.

In: Cancer Research, Vol. 70, No. 13, 01.07.2010, p. 5628-5638.

Research output: Contribution to journalArticle

Kalea, Anastasia Z. ; See, Fiona ; Harja, Evis ; Arriero, Maria ; Schmidt, Ann Marie ; Hudson, Barry. / Alternatively sliced RAGEv1 inhibits tumorigenesis through suppression of JNK signaling. In: Cancer Research. 2010 ; Vol. 70, No. 13. pp. 5628-5638.
@article{c0aa14a836cc43b3b9cca1f4de509856,
title = "Alternatively sliced RAGEv1 inhibits tumorigenesis through suppression of JNK signaling",
abstract = "Receptor for advanced glycation end products (RAGE) and its ligands are overexpressed in multiple cancers. RAGE has been implicated in tumorigenesis and metastasis, but little is known of the mechanisms involved. In this study, we define a specific functional role for an alternate splice variant termed RAGE splice variant 1 (RAGEv1), which encodes a soluble endogenous form of the receptor that inhibits tumorigenesis. RAGEv1 was downregulated in lung, prostate, and brain tumors relative to control matched tissues. Overexpressing RAGEv1 in tumor cells altered RAGE ligand stimulation of several novel classes of genes that are critical in tumorigenesis and metastasis. Additionally, RAGEv1 inhibited tumor formation, cell invasion, and angiogenesis induced by RAGE ligand signaling. Analysis of signal transduction pathways underlying these effects revealed marked suppression of c-jun-NH2-kinase (JNK) pathway signaling, and JNK inhibition suppressed signaling through the RAGE pathway. Tumors expressing RAGEv1 were significantly smaller than wild-type tumors and displayed prominently reduced activation of JNK. Our results identify RAGEv1 as a novel suppressor, the study of which may offer new cancer therapeutic directions.",
author = "Kalea, {Anastasia Z.} and Fiona See and Evis Harja and Maria Arriero and Schmidt, {Ann Marie} and Barry Hudson",
year = "2010",
month = "7",
day = "1",
doi = "10.1158/0008-5472.CAN-10-0595",
language = "English",
volume = "70",
pages = "5628--5638",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "13",

}

TY - JOUR

T1 - Alternatively sliced RAGEv1 inhibits tumorigenesis through suppression of JNK signaling

AU - Kalea, Anastasia Z.

AU - See, Fiona

AU - Harja, Evis

AU - Arriero, Maria

AU - Schmidt, Ann Marie

AU - Hudson, Barry

PY - 2010/7/1

Y1 - 2010/7/1

N2 - Receptor for advanced glycation end products (RAGE) and its ligands are overexpressed in multiple cancers. RAGE has been implicated in tumorigenesis and metastasis, but little is known of the mechanisms involved. In this study, we define a specific functional role for an alternate splice variant termed RAGE splice variant 1 (RAGEv1), which encodes a soluble endogenous form of the receptor that inhibits tumorigenesis. RAGEv1 was downregulated in lung, prostate, and brain tumors relative to control matched tissues. Overexpressing RAGEv1 in tumor cells altered RAGE ligand stimulation of several novel classes of genes that are critical in tumorigenesis and metastasis. Additionally, RAGEv1 inhibited tumor formation, cell invasion, and angiogenesis induced by RAGE ligand signaling. Analysis of signal transduction pathways underlying these effects revealed marked suppression of c-jun-NH2-kinase (JNK) pathway signaling, and JNK inhibition suppressed signaling through the RAGE pathway. Tumors expressing RAGEv1 were significantly smaller than wild-type tumors and displayed prominently reduced activation of JNK. Our results identify RAGEv1 as a novel suppressor, the study of which may offer new cancer therapeutic directions.

AB - Receptor for advanced glycation end products (RAGE) and its ligands are overexpressed in multiple cancers. RAGE has been implicated in tumorigenesis and metastasis, but little is known of the mechanisms involved. In this study, we define a specific functional role for an alternate splice variant termed RAGE splice variant 1 (RAGEv1), which encodes a soluble endogenous form of the receptor that inhibits tumorigenesis. RAGEv1 was downregulated in lung, prostate, and brain tumors relative to control matched tissues. Overexpressing RAGEv1 in tumor cells altered RAGE ligand stimulation of several novel classes of genes that are critical in tumorigenesis and metastasis. Additionally, RAGEv1 inhibited tumor formation, cell invasion, and angiogenesis induced by RAGE ligand signaling. Analysis of signal transduction pathways underlying these effects revealed marked suppression of c-jun-NH2-kinase (JNK) pathway signaling, and JNK inhibition suppressed signaling through the RAGE pathway. Tumors expressing RAGEv1 were significantly smaller than wild-type tumors and displayed prominently reduced activation of JNK. Our results identify RAGEv1 as a novel suppressor, the study of which may offer new cancer therapeutic directions.

UR - http://www.scopus.com/inward/record.url?scp=77954350266&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954350266&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-10-0595

DO - 10.1158/0008-5472.CAN-10-0595

M3 - Article

C2 - 20570900

AN - SCOPUS:77954350266

VL - 70

SP - 5628

EP - 5638

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 13

ER -