TRAF6 is an amplified oncogene bridging the RAS and NF-κB pathways in human lung cancer

Daniel T. Starczynowski, William W. Lockwood, Sophie Deléhouzée, Raj Chari, Joanna Wegrzyn, Megan Fuller, Ming Sound Tsao, Stephen Lam, Adi F. Gazdar, Wan L. Lam, Aly Karsan

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Somatic mutations and copy number alterations (as a result of deletion or amplification of large portions of a chromosome) are major drivers of human lung cancers. Detailed analysis of lung cancer - associated chromosomal amplifications could identify novel oncogenes. By performing an integrative cytogenetic and gene expression analysis of non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) cell lines and tumors, we report here the identification of a frequently recurring amplification at chromosome 11 band p13. Within this region, only TNF receptor - associated factor 6 (TRAF6) exhibited concomitant mRNA overexpression and gene amplification in lung cancers. Inhibition of TRAF6 in human lung cancer cell lines suppressed NF-κB activation, anchorage-independent growth, and tumor formation. In these lung cancer cell lines, RAS required TRAF6 for its oncogenic capabilities. Furthermore, TRAF6 overexpression in NIH3T3 cells resulted in NF-κB activation, anchorage-independent growth, and tumor formation. Our findings show that TRAF6 is an oncogene that is important for RAS-mediated oncogenesis and provide a mechanistic explanation for the previously apparent importance of constitutive NF-κB activation in RAS-driven lung cancers.

Original languageEnglish (US)
Pages (from-to)4095-4105
Number of pages11
JournalJournal of Clinical Investigation
Volume121
Issue number10
DOIs
StatePublished - Oct 3 2011

Fingerprint

TNF Receptor-Associated Factor 6
Oncogenes
Lung Neoplasms
Cell Line
Chromosomes, Human, Pair 11
Gene Amplification
Small Cell Lung Carcinoma
Growth
Tumor Cell Line
Non-Small Cell Lung Carcinoma
Cytogenetics
Neoplasms
Carcinogenesis
Chromosomes
Gene Expression
Messenger RNA
Mutation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Starczynowski, D. T., Lockwood, W. W., Deléhouzée, S., Chari, R., Wegrzyn, J., Fuller, M., ... Karsan, A. (2011). TRAF6 is an amplified oncogene bridging the RAS and NF-κB pathways in human lung cancer. Journal of Clinical Investigation, 121(10), 4095-4105. https://doi.org/10.1172/JCI58818

TRAF6 is an amplified oncogene bridging the RAS and NF-κB pathways in human lung cancer. / Starczynowski, Daniel T.; Lockwood, William W.; Deléhouzée, Sophie; Chari, Raj; Wegrzyn, Joanna; Fuller, Megan; Tsao, Ming Sound; Lam, Stephen; Gazdar, Adi F.; Lam, Wan L.; Karsan, Aly.

In: Journal of Clinical Investigation, Vol. 121, No. 10, 03.10.2011, p. 4095-4105.

Research output: Contribution to journalArticle

Starczynowski, DT, Lockwood, WW, Deléhouzée, S, Chari, R, Wegrzyn, J, Fuller, M, Tsao, MS, Lam, S, Gazdar, AF, Lam, WL & Karsan, A 2011, 'TRAF6 is an amplified oncogene bridging the RAS and NF-κB pathways in human lung cancer', Journal of Clinical Investigation, vol. 121, no. 10, pp. 4095-4105. https://doi.org/10.1172/JCI58818
Starczynowski DT, Lockwood WW, Deléhouzée S, Chari R, Wegrzyn J, Fuller M et al. TRAF6 is an amplified oncogene bridging the RAS and NF-κB pathways in human lung cancer. Journal of Clinical Investigation. 2011 Oct 3;121(10):4095-4105. https://doi.org/10.1172/JCI58818
Starczynowski, Daniel T. ; Lockwood, William W. ; Deléhouzée, Sophie ; Chari, Raj ; Wegrzyn, Joanna ; Fuller, Megan ; Tsao, Ming Sound ; Lam, Stephen ; Gazdar, Adi F. ; Lam, Wan L. ; Karsan, Aly. / TRAF6 is an amplified oncogene bridging the RAS and NF-κB pathways in human lung cancer. In: Journal of Clinical Investigation. 2011 ; Vol. 121, No. 10. pp. 4095-4105.
@article{263e7ab0f941402389e4ec960a3c0b7d,
title = "TRAF6 is an amplified oncogene bridging the RAS and NF-κB pathways in human lung cancer",
abstract = "Somatic mutations and copy number alterations (as a result of deletion or amplification of large portions of a chromosome) are major drivers of human lung cancers. Detailed analysis of lung cancer - associated chromosomal amplifications could identify novel oncogenes. By performing an integrative cytogenetic and gene expression analysis of non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) cell lines and tumors, we report here the identification of a frequently recurring amplification at chromosome 11 band p13. Within this region, only TNF receptor - associated factor 6 (TRAF6) exhibited concomitant mRNA overexpression and gene amplification in lung cancers. Inhibition of TRAF6 in human lung cancer cell lines suppressed NF-κB activation, anchorage-independent growth, and tumor formation. In these lung cancer cell lines, RAS required TRAF6 for its oncogenic capabilities. Furthermore, TRAF6 overexpression in NIH3T3 cells resulted in NF-κB activation, anchorage-independent growth, and tumor formation. Our findings show that TRAF6 is an oncogene that is important for RAS-mediated oncogenesis and provide a mechanistic explanation for the previously apparent importance of constitutive NF-κB activation in RAS-driven lung cancers.",
author = "Starczynowski, {Daniel T.} and Lockwood, {William W.} and Sophie Del{\'e}houz{\'e}e and Raj Chari and Joanna Wegrzyn and Megan Fuller and Tsao, {Ming Sound} and Stephen Lam and Gazdar, {Adi F.} and Lam, {Wan L.} and Aly Karsan",
year = "2011",
month = "10",
day = "3",
doi = "10.1172/JCI58818",
language = "English (US)",
volume = "121",
pages = "4095--4105",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "10",

}

TY - JOUR

T1 - TRAF6 is an amplified oncogene bridging the RAS and NF-κB pathways in human lung cancer

AU - Starczynowski, Daniel T.

AU - Lockwood, William W.

AU - Deléhouzée, Sophie

AU - Chari, Raj

AU - Wegrzyn, Joanna

AU - Fuller, Megan

AU - Tsao, Ming Sound

AU - Lam, Stephen

AU - Gazdar, Adi F.

AU - Lam, Wan L.

AU - Karsan, Aly

PY - 2011/10/3

Y1 - 2011/10/3

N2 - Somatic mutations and copy number alterations (as a result of deletion or amplification of large portions of a chromosome) are major drivers of human lung cancers. Detailed analysis of lung cancer - associated chromosomal amplifications could identify novel oncogenes. By performing an integrative cytogenetic and gene expression analysis of non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) cell lines and tumors, we report here the identification of a frequently recurring amplification at chromosome 11 band p13. Within this region, only TNF receptor - associated factor 6 (TRAF6) exhibited concomitant mRNA overexpression and gene amplification in lung cancers. Inhibition of TRAF6 in human lung cancer cell lines suppressed NF-κB activation, anchorage-independent growth, and tumor formation. In these lung cancer cell lines, RAS required TRAF6 for its oncogenic capabilities. Furthermore, TRAF6 overexpression in NIH3T3 cells resulted in NF-κB activation, anchorage-independent growth, and tumor formation. Our findings show that TRAF6 is an oncogene that is important for RAS-mediated oncogenesis and provide a mechanistic explanation for the previously apparent importance of constitutive NF-κB activation in RAS-driven lung cancers.

AB - Somatic mutations and copy number alterations (as a result of deletion or amplification of large portions of a chromosome) are major drivers of human lung cancers. Detailed analysis of lung cancer - associated chromosomal amplifications could identify novel oncogenes. By performing an integrative cytogenetic and gene expression analysis of non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) cell lines and tumors, we report here the identification of a frequently recurring amplification at chromosome 11 band p13. Within this region, only TNF receptor - associated factor 6 (TRAF6) exhibited concomitant mRNA overexpression and gene amplification in lung cancers. Inhibition of TRAF6 in human lung cancer cell lines suppressed NF-κB activation, anchorage-independent growth, and tumor formation. In these lung cancer cell lines, RAS required TRAF6 for its oncogenic capabilities. Furthermore, TRAF6 overexpression in NIH3T3 cells resulted in NF-κB activation, anchorage-independent growth, and tumor formation. Our findings show that TRAF6 is an oncogene that is important for RAS-mediated oncogenesis and provide a mechanistic explanation for the previously apparent importance of constitutive NF-κB activation in RAS-driven lung cancers.

UR - http://www.scopus.com/inward/record.url?scp=80053389114&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80053389114&partnerID=8YFLogxK

U2 - 10.1172/JCI58818

DO - 10.1172/JCI58818

M3 - Article

VL - 121

SP - 4095

EP - 4105

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 10

ER -