A functional mammalian target of rapamycin complex 1 signaling is indispensable for c‐Myc‐driven hepatocarcinogenesis

• DOI: 10.1002/hep.29183
• Publication Date: 2017-03-30T10:31:54Z
• Authors: Pin Liu; Mengmeng Ge; Junjie Hu; Xiaolei Li; Li Che; Kun Sun; Lili Cheng; Yuedong Huang; Maria G. Pilo; Antonio Cigliano; Giovanni M. Pes; Rosa M. Pascale; Stefania Brozzetti; Gianpaolo Vidili; Alberto Porcu; Antonio Cossu; Giuseppe Palmieri; Maria C. Sini; Silvia Ribback; Frank Dombrowski; Junyan Tao; Diego F. Calvisi; Ligong Chen; Xin Chen
• Keywords: Ribosomal protein s6

Amplification and/or activation of the c‐Myc proto‐oncogene is one leading genetic events along hepatocarcinogenesis. The oncogenic potential has been proven experimentally by finding that its overexpression in mouse liver triggers tumor formation. However, molecular mechanism whereby exerts activity remains poorly understood. Here, we demonstrate mammalian target rapamycin complex 1 (mTORC1) cascade activated and necessary for c‐Myc‐dependent Specifically, found ablation Raptor , unique member mTORC1, strongly inhibits Also, p70 ribosomal S6 kinase/ribosomal protein eukaryotic translation initiation factor 4E‐binding 1/eukaryotic 4E signaling cascades downstream mTORC1 are required c‐Myc‐driven tumorigenesis. Intriguingly, microarray expression analysis revealed up‐regulation multiple amino acid transporters, including solute carrier family A5 (SLC1A5) SLC7A6, to robust uptake acids, glutamine, into cells. Subsequent functional studies showed acids critical as their inhibition suppressed In human hepatocellular carcinoma specimens, levels directly correlate with those well SLC1A5 SLC7A6. Conclusion : Our current study indicates an intact axis hepatocarcinogenesis; thus, targeting mTOR pathway or transporters may be effective novel therapeutic option treatment signaling. (H epatology 2017;66:167–181).