TRAF4 is a critical molecule for Akt activation in lung cancer

Wei Li, Cong Peng, Mee Hyun Lee, Do Young Lim, Feng Zhu, Yang Fu, Ge Yang, Yuqiao Sheng, Lanbo Xiao, Xin Dong, Wei-Ya Ma, Ann M. Bode, Ya Cao, Zigang Dong

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

TRAF4 is an adapter protein overexpressed in certain cancers, but its contributions to tumorigenesis are unclear. In lung cancer cells and primary lung tumors, we found that TRAF4 is overexpressed. RNA interference-mediated attenuation of TRAF4 expression blunted the malignant phenotype in this setting, exerting inhibitory effects on cell proliferation, anchorage-independent growth, and tumor development in a xenograft mouse model. Unexpectedly, we discovered that TRAF4, but not Skp2, was required for activation of the pivotal cell survival kinase Akt through ubiquitination. Furthermore, TRAF4 attenuation impaired glucose metabolism by inhibiting expression of Glut1 and HK2 mediated by the Akt pathway. Overall, our work suggests that TRAF4 offers a candidate molecular target for lung cancer prevention and therapy.

Original languageEnglish (US)
Pages (from-to)6938-6950
Number of pages13
JournalCancer Research
Volume73
Issue number23
DOIs
StatePublished - Dec 1 2013

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  • Cite this

    Li, W., Peng, C., Lee, M. H., Lim, D. Y., Zhu, F., Fu, Y., Yang, G., Sheng, Y., Xiao, L., Dong, X., Ma, W-Y., Bode, A. M., Cao, Y., & Dong, Z. (2013). TRAF4 is a critical molecule for Akt activation in lung cancer. Cancer Research, 73(23), 6938-6950. https://doi.org/10.1158/0008-5472.CAN-13-0913