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.
authors.affiliation: Authors' Affiliations: The Hormel Institute, University of Minnesota, Austin, Minnesota; Cancer Research Institute, Xiangya School of Medicine; Xiangya Hospital, Central South University, Changsha, Hunan; The First Affiliated Hospital; and Physiology and Pathophysiology, Basic Medical School, Zhengzhou University, Zhengzhou, Henan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Cong
authors.initials: C
authors.lastname: Peng
authors.forename: Mee-Hyun
authors.initials: MH
authors.lastname: Lee
authors.forename: DoYoung
authors.initials: D
authors.lastname: Lim
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Yang
authors.initials: Y
authors.lastname: Fu
authors.forename: Ge
authors.initials: G
authors.lastname: Yang
authors.forename: Yuqiao
authors.initials: Y
authors.lastname: Sheng
authors.forename: Lanbo
authors.initials: L
authors.lastname: Xiao
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.forename: WeiYa
authors.initials: W
authors.lastname: Ma
authors.forename: Ann M
authors.initials: AM
authors.lastname: Bode
authors.forename: Ya
authors.initials: Y
authors.lastname: Cao
authors.forename: Zigang
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D053449:TNF Receptor-Associated Factor 4 / Q000037:antagonists & inhibitors / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D053449:TNF Receptor-Associated Factor 4; C506367:TRAF4 protein, human; D051058:Oncogene Protein v-akt