TRAF2 is an NF-κB-activating oncogene in epithelial cancers

被引：55

作者：

Shen, R. R. ^{[1
,2
,3
]}

Zhou, A. Y. ^{[1
,2
,3
]}

Kim, E. ^{[1
,2
,3
]}

O'Connell, J. T. ^{[1
,2
,3
]}

Hagerstrand, D. ^{[1
,2
,3
]}

Beroukhim, R. ^{[1
,2
,3
]}

Hahn, W. C. ^{[1
,2
,3
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[2] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA

[3] Broad Inst Harvard & MIT, Cambridge, MA USA

来源：

ONCOGENE | 2015年 / 34卷 / 02期

关键词：

TRAF2; NF-kappa B; cancer; 9q34; amplification; TUMOR-SUPPRESSOR CYLD; K63-LINKED POLYUBIQUITINATION; MULTIPLE-MYELOMA; CELL LYMPHOMA; MOUSE MODEL; IKK; PHOSPHORYLATION; TUMORIGENESIS; MUTATIONS; PATHWAY;

D O I：

10.1038/onc.2013.543

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Aberrant nuclear factor (NF)-kappa B activation is frequently observed in human cancers. Genome characterization efforts have identified genetic alterations in multiple components of the NF-kappa B 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-kappa B 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-kappa B activation, anchorage-independent growth and tumorigenesis. Cancer cells that are dependent on TRAF2 also require NF-kappa B 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.

引用

页码：209 / 216

页数：8

共 43 条

[1] NF-κB in Cancer: A Matter of Life and Death [J].

Aggarwal, Bharat B. ;

Sung, Bokyung .

CANCER DISCOVERY, 2011, 1 (06) :469-471

[2] Frequent engagement of the classical and alternative NF-κB pathways by diverse genetic abnormalities in multiple myeloma [J].

Annunziata, Christina M. ;

Davis, R. Eric ;

Demchenko, Yulia ;

Bellamy, William ;

Gabrea, Ana ;

Zhan, Fenghuang ;

Lenz, Georg ;

Hanamura, Ichiro ;

Wright, George ;

Xiao, Wenming ;

Dave, Sandeep ;

Hurt, Elaine M. ;

Tan, Bruce ;

Zhao, Hong ;

Stephens, Owen ;

Santra, Madhumita ;

Williams, David R. ;

Dang, Lenny ;

Barlogie, Bart ;

Shaughnessy, John D., Jr. ;

Kuehl, W. Michael ;

Staudt, Louis M. .

CANCER CELL, 2007, 12 (02) :115-130

[3] Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1 [J].

Barbie, David A. ;

Tamayo, Pablo ;

Boehm, Jesse S. ;

Kim, So Young ;

Moody, Susan E. ;

Dunn, Ian F. ;

Schinzel, Anna C. ;

Sandy, Peter ;

Meylan, Etienne ;

Scholl, Claudia ;

Froehling, Stefan ;

Chan, Edmond M. ;

Sos, Martin L. ;

Michel, Kathrin ;

Mermel, Craig ;

Silver, Serena J. ;

Weir, Barbara A. ;

Reiling, Jan H. ;

Sheng, Qing ;

Gupta, Piyush B. ;

Wadlow, Raymond C. ;

Le, Hanh ;

Hoersch, Sebastian ;

Wittner, Ben S. ;

Ramaswamy, Sridhar ;

Livingston, David M. ;

Sabatini, David M. ;

Meyerson, Matthew ;

Thomas, Roman K. ;

Lander, Eric S. ;

Mesirov, Jill P. ;

Root, David E. ;

Gilliland, D. Gary ;

Jacks, Tyler ;

Hahn, William C. .

NATURE, 2009, 462 (7269) :108-U122

[4] The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity [J].

Barretina, Jordi ;

Caponigro, Giordano ;

Stransky, Nicolas ;

Venkatesan, Kavitha ;

Margolin, Adam A. ;

Kim, Sungjoon ;

Wilson, Christopher J. ;

Lehar, Joseph ;

Kryukov, Gregory V. ;

Sonkin, Dmitriy ;

Reddy, Anupama ;

Liu, Manway ;

Murray, Lauren ;

Berger, Michael F. ;

Monahan, John E. ;

Morais, Paula ;

Meltzer, Jodi ;

Korejwa, Adam ;

Jane-Valbuena, Judit ;

Mapa, Felipa A. ;

Thibault, Joseph ;

Bric-Furlong, Eva ;

Raman, Pichai ;

Shipway, Aaron ;

Engels, Ingo H. ;

Cheng, Jill ;

Yu, Guoying K. ;

Yu, Jianjun ;

Aspesi, Peter, Jr. ;

de Silva, Melanie ;

Jagtap, Kalpana ;

Jones, Michael D. ;

Wang, Li ;

Hatton, Charles ;

Palescandolo, Emanuele ;

Gupta, Supriya ;

Mahan, Scott ;

Sougnez, Carrie ;

Onofrio, Robert C. ;

Liefeld, Ted ;

MacConaill, Laura ;

Winckler, Wendy ;

Reich, Michael ;

Li, Nanxin ;

Mesirov, Jill P. ;

Gabriel, Stacey B. ;

Getz, Gad ;

Ardlie, Kristin ;

Chan, Vivien ;

Myer, Vic E. .

NATURE, 2012, 483 (7391) :603-607

[5] Requirement of the NF-κB Subunit p65/RelA for K-Ras-Induced Lung Tumorigenesis [J].

Basseres, Daniela S. ;

Ebbs, Aaron ;

Levantini, Elena ;

Baldwin, Albert S. .

CANCER RESEARCH, 2010, 70 (09) :3537-3546

[6] Histone H2AX: A dosage-dependent suppressor of oncogenic translocations and tumors [J].

Bassing, CH ;

Suh, H ;

Ferguson, DO ;

Chua, KF ;

Manis, J ;

Eckersdorff, M ;

Gleason, M ;

Bronson, R ;

Lee, C ;

Alt, FW .

CELL, 2003, 114 (03) :359-370

[7] OPINION Is NF-κB a good target for cancer therapy? Hopes and pitfalls [J].

Baud, Veronique ;

Karin, Michael .

NATURE REVIEWS DRUG DISCOVERY, 2009, 8 (01) :33-40

[8] Integrated genomic analyses of ovarian carcinoma [J].

Bell, D. ;

Berchuck, A. ;

Birrer, M. ;

Chien, J. ;

Cramer, D. W. ;

Dao, F. ;

Dhir, R. ;

DiSaia, P. ;

Gabra, H. ;

Glenn, P. ;

Godwin, A. K. ;

Gross, J. ;

Hartmann, L. ;

Huang, M. ;

Huntsman, D. G. ;

Iacocca, M. ;

Imielinski, M. ;

Kalloger, S. ;

Karlan, B. Y. ;

Levine, D. A. ;

Mills, G. B. ;

Morrison, C. ;

Mutch, D. ;

Olvera, N. ;

Orsulic, S. ;

Park, K. ;

Petrelli, N. ;

Rabeno, B. ;

Rader, J. S. ;

Sikic, B. I. ;

Smith-McCune, K. ;

Sood, A. K. ;

Bowtell, D. ;

Penny, R. ;

Testa, J. R. ;

Chang, K. ;

Dinh, H. H. ;

Drummond, J. A. ;

Fowler, G. ;

Gunaratne, P. ;

Hawes, A. C. ;

Kovar, C. L. ;

Lewis, L. R. ;

Morgan, M. B. ;

Newsham, I. F. ;

Santibanez, J. ;

Reid, J. G. ;

Trevino, L. R. ;

Wu, Y. -Q. ;

Wang, M. .

NATURE, 2011, 474 (7353) :609-615

[9] The landscape of somatic copy-number alteration across human cancers [J].

Beroukhim, Rameen ;

Mermel, Craig H. ;

Porter, Dale ;

Wei, Guo ;

Raychaudhuri, Soumya ;

Donovan, Jerry ;

Barretina, Jordi ;

Boehm, Jesse S. ;

Dobson, Jennifer ;

Urashima, Mitsuyoshi ;

Mc Henry, Kevin T. ;

Pinchback, Reid M. ;

Ligon, Azra H. ;

Cho, Yoon-Jae ;

Haery, Leila ;

Greulich, Heidi ;

Reich, Michael ;

Winckler, Wendy ;

Lawrence, Michael S. ;

Weir, Barbara A. ;

Tanaka, Kumiko E. ;

Chiang, Derek Y. ;

Bass, Adam J. ;

Loo, Alice ;

Hoffman, Carter ;

Prensner, John ;

Liefeld, Ted ;

Gao, Qing ;

Yecies, Derek ;

Signoretti, Sabina ;

Maher, Elizabeth ;

Kaye, Frederic J. ;

Sasaki, Hidefumi ;

Tepper, Joel E. ;

Fletcher, Jonathan A. ;

Tabernero, Josep ;

Baselga, Jose ;

Tsao, Ming-Sound ;

Demichelis, Francesca ;

Rubin, Mark A. ;

Janne, Pasi A. ;

Daly, Mark J. ;

Nucera, Carmelo ;

Levine, Ross L. ;

Ebert, Benjamin L. ;

Gabriel, Stacey ;

Rustgi, Anil K. ;

Antonescu, Cristina R. ;

Ladanyi, Marc ;

Letai, Anthony .

NATURE, 2010, 463 (7283) :899-905

[10]

Billie Au PY, 2007, ADV EXP MED BIOL, V597, P32

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