title: TRAF2 is an NF-κB-activating oncogene in epithelial cancers.
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.
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [3] Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Shen
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [3] Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: A Y
authors.initials: AY
authors.lastname: Zhou
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [3] Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Kim
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [3] Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: O'Connell
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [3] Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hagerstrand
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [3] Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Beroukhim
authors.affiliation: 1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [3] Broad Institute of Harvard and MIT, Cambridge, MA, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Hahn
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism*; D009857:Oncogenes; D010766:Phosphorylation; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D047992:TNF Receptor-Associated Factor 2