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

doi:10.1158/0008-5472.CAN-13-0913

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

Hormel Institute

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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 language	English (US)
Pages (from-to)	6938-6950
Number of pages	13
Journal	Cancer Research
Volume	73
Issue number	23
DOIs	https://doi.org/10.1158/0008-5472.CAN-13-0913
State	Published - Dec 1 2013

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title = "TRAF4 is a critical molecule for Akt activation in lung cancer",

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.",

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T1 - TRAF4 is a critical molecule for Akt activation in lung cancer

AU - Li, Wei

AU - Peng, Cong

AU - Lee, Mee Hyun

AU - Lim, Do Young

AU - Zhu, Feng

AU - Fu, Yang

AU - Yang, Ge

AU - Sheng, Yuqiao

AU - Xiao, Lanbo

AU - Dong, Xin

AU - Ma, Wei-Ya

AU - Bode, Ann M.

AU - Cao, Ya

AU - Dong, Zigang

PY - 2013/12/1

Y1 - 2013/12/1

N2 - 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.

AB - 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.

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TRAF4 is a critical molecule for Akt activation in lung cancer

Abstract

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