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

Daniel T Starczynowski1, William W Lockwood, Sophie Deléhouzée

  • 1British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

The Journal of Clinical Investigation
|September 14, 2011
PubMed

Insights

Tumorigenesis in lung cancer is driven by gene amplifications. Researchers identified Tumor Necrosis Factor Receptor Associated Factor 6 (TRAF6) as a key oncogene, crucial for RAS-mediated lung cancer development.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Somatic mutations and copy number alterations are primary drivers of human lung cancers.
  • Analyzing chromosomal amplifications in lung cancer may reveal novel oncogenes.

Purpose of the Study:

  • To identify novel oncogenes by analyzing chromosomal amplifications in lung cancer.
  • To investigate the role of Tumor Necrosis Factor Receptor Associated Factor 6 (TRAF6) in lung cancer development.

Main Methods:

  • Integrative cytogenetic and gene expression analysis of non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) cell lines and tumors.
  • Inhibition of TRAF6 in lung cancer cell lines.
  • Overexpression of TRAF6 in NIH3T3 cells.

Main Results:

  • A recurring amplification at chromosome 11 band p13 was identified, with TRAF6 showing both gene amplification and mRNA overexpression in lung cancers.
  • TRAF6 inhibition suppressed NF-κB activation, anchorage-independent growth, and tumor formation in lung cancer cell lines.
  • TRAF6 is essential for RAS oncogenic activity and promotes NF-κB activation, anchorage-independent growth, and tumor formation upon overexpression.

Conclusions:

  • TRAF6 functions as an oncogene in lung cancer.
  • TRAF6 plays a critical role in RAS-mediated oncogenesis.
  • TRAF6 activation provides a mechanistic link between RAS signaling and constitutive NF-κB activation in lung cancer.

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