Shen R R, Zhou A Y, Kim E, O'Connell J T, Hagerstrand D, Beroukhim R, Hahn W C
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.
Oncogene. 2015 Jan 8;34(2):209-16. doi: 10.1038/onc.2013.543. Epub 2013 Dec 23.
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.
异常的核因子（NF）-κB激活在人类癌症中经常被观察到。基因组特征分析工作已经确定了NF-κB信号通路多个组分中的基因改变，其中一些已被证明对癌症的起始和肿瘤维持至关重要。在这里，我们使用患者肿瘤和癌细胞系，确定NF-κB调节因子TRAF2（肿瘤坏死因子（TNF）受体相关因子2）是一种癌基因，在15%的人类上皮癌中反复发生扩增和重排。在携带TRAF2拷贝数增加的癌细胞中抑制TRAF2可抑制增殖、NF-κB激活、非锚定依赖性生长和肿瘤发生。依赖TRAF2的癌细胞生存也需要NF-κB。TRAF2丝氨酸11位点的磷酸化对于携带TRAF2扩增的癌细胞的生存至关重要。这些观察结果共同确定TRAF2是一种经常扩增的癌基因。
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