title: c-MYC overexpression overrides TAK1 dependency in efficient tumorigenicity of AKT-transformed cells.
abstract: Transforming growth factor activated kinase 1 (TAK1) provides prosurvival signals in various types of cells, and emerging evidence indicates that targeting TAK1 is a promising means to eliminate certain types of cancer cells. Here, we show that TAK1 is required for efficient tumorigenicity of AKT-transformed cells. TAK1 inhibition accelerates cell apoptosis of AKT-transformed cells in anchorage-independent cell growth accompanying by the downregulation of Mcl-1 and Bcl-2 expression. On the contrary, the tumorigenicity of c-Myc-transformed cells is not significantly affected by TAK1 inhibition. Moreover, AKT-transformed cells with c-Myc overexpression tolerate TAK1 inhibition in anchorage-independent growth and tumorigenicity in vivo. Together, our results provide evidence that TAK1-dependency in the tumorigenicity of AKT-transformed cells can be alleviated by c-Myc overexpression. These findings suggest that dual-targeting TAK1 and c-Myc might be a rational therapeutic strategy for treatment of certain types of cancer.
authors.affiliation: Medical School of Fudan University, Shanghai, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Qu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Aihui
authors.initials: A
authors.lastname: Ma
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Jingyi
authors.initials: J
authors.lastname: Li
authors.forename: Dongxu
authors.initials: D
authors.lastname: Xu
authors.forename: Zhaojuan
authors.initials: Z
authors.lastname: Yang
authors.forename: Wenxin
authors.initials: W
authors.lastname: Qin
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D053200:Fas-Associated Death Domain Protein; D020930:MAP Kinase Kinase Kinases; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D053221:TNF-Related Apoptosis-Inducing Ligand; D000099151:MAP Kinase Kinase Kinase 7