Abstract
Aberrant nuclear factor (NF)-κB activation is frequently observed in human cancers. Genome characterization efforts have identified genetic alterations in multiple components of the NF-κB pathway, some of which have been shown to be essential for cancer initiation and tumor maintenance. Here, using patient tumors and cancer cell lines, we identify the NF-κB regulator, TRAF2 (tumor necrosis factor (TNF) receptor-associated factor 2), as an oncogene that is recurrently amplified and rearranged in 15% of human epithelial cancers. Suppression of TRAF2 in cancer cells harboring TRAF2 copy number gain inhibits proliferation, NF-κB activation, anchorage-independent growth and tumorigenesis. Cancer cells that are dependent on TRAF2 also require NF-κB for survival. The phosphorylation of TRAF2 at serine 11 is essential for the survival of cancer cells harboring TRAF2 amplification. Together, these observations identify TRAF2 as a frequently amplified oncogene.
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Acknowledgements
We thank members of the Hahn lab and the Cichowski lab for thoughtful discussion, reagents and technical assistance. We also thank Hasem Habelhah for providing the pTRAF2 (Ser11) antibody. We further thank Shumei Wang, Anita Hawkins, Chengzeng Zhang and Cynthia Morton at the DFCI Cytogenetics Core for TRAF2 FISH analysis and discussion. This work was supported in part by R01 CA130988 (to WCH), a Ruth L. Kirschstein National Research Service Award F32 CA128265 (to RRS) and The Aid for Cancer Research (to RRS).
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RB and WCH are consultants for Novartis. The remaining authors declare no conflicts of interest.
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Shen, R., Zhou, A., Kim, E. et al. TRAF2 is an NF-κB-activating oncogene in epithelial cancers. Oncogene 34, 209–216 (2015). https://doi.org/10.1038/onc.2013.543
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DOI: https://doi.org/10.1038/onc.2013.543
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