Difference between revisions of "Wang 2016 J Biol Chem"
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|title=Wang H, Lu J, Edmunds LR, Kulkarni S, Dolezal J, Tao J, Ranganathan S, Jackson L, Fromherz M, Stolz DB, Uppala R, Bharathi S, Monga SP, Goetzman ES, Prochownik EV (2016) Coordinated activities of multiple Myc-dependent and Myc-independent biosynthetic pathways in Hepatoblastoma. J Biol Chem 291:26241-51. | |title=Wang H, Lu J, Edmunds LR, Kulkarni S, Dolezal J, Tao J, Ranganathan S, Jackson L, Fromherz M, Stolz DB, Uppala R, Bharathi S, Monga SP, Goetzman ES, Prochownik EV (2016) Coordinated activities of multiple Myc-dependent and Myc-independent biosynthetic pathways in Hepatoblastoma. J Biol Chem 291:26241-51. | ||
|info=[https://www.ncbi.nlm.nih.gov/pubmed/27738108 PMID: 27738108 Open Access] | |info=[https://www.ncbi.nlm.nih.gov/pubmed/27738108 PMID: 27738108 Open Access] | ||
|authors=Wang H, Lu J, Edmunds LR, Kulkarni S, Dolezal J, Tao J, Ranganathan S, Jackson L, Fromherz M, Stolz DB, Uppala R, Bharathi S, Monga SP, Goetzman | |authors=Wang H, Lu J, Edmunds LR, Kulkarni S, Dolezal J, Tao J, Ranganathan S, Jackson L, Fromherz M, Stolz DB, Uppala R, Bharathi Sivakama S, Monga SP, Goetzman Eric S, Prochownik EV | ||
|year=2016 | |year=2016 | ||
|journal=J Biol Chem | |journal=J Biol Chem | ||
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|pathways=N, S, NS | |pathways=N, S, NS | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=2016-11, | |additional=2016-11, US | ||
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Latest revision as of 17:55, 29 February 2020
Wang H, Lu J, Edmunds LR, Kulkarni S, Dolezal J, Tao J, Ranganathan S, Jackson L, Fromherz M, Stolz DB, Uppala R, Bharathi S, Monga SP, Goetzman ES, Prochownik EV (2016) Coordinated activities of multiple Myc-dependent and Myc-independent biosynthetic pathways in Hepatoblastoma. J Biol Chem 291:26241-51. |
Wang H, Lu J, Edmunds LR, Kulkarni S, Dolezal J, Tao J, Ranganathan S, Jackson L, Fromherz M, Stolz DB, Uppala R, Bharathi Sivakama S, Monga SP, Goetzman Eric S, Prochownik EV (2016) J Biol Chem
Abstract: Hepatoblastoma (HB) is associated with aberrant activation of the ฮฒ-catenin and Hippo/YAP signaling pathways. Over-expression of mutant ฮฒ-catenin and YAP in mice induces HBs that express high levels of c-Myc (Myc). In light of recent observations that Myc in unnecessary for long-term hepatocyte proliferation, we have now examined its role in HB pathogenesis using the above model. While Myc was found to be dispensable for in vivo HB initiation it was necessary to sustain rapid tumor growth. Gene expression profiling identified key molecular differences between myc+/+ (WT) and myc-/- (KO) hepatocytes and HBs that explain these behaviors. In HBs, these included both Myc-dependent and Myc-independent increases in families of transcripts encoding ribosomal proteins, non-structural factors affecting ribosome assembly and function and enzymes catalyzing glycolysis, lipid bio-synthesis and fatty acid ฮฒ-oxidation. Myc-independent metabolic changes associated with HBs included dramatic reductions in mitochondrial mass and oxidative function and increases in ATP content and pyruvate dehydrogenase activity. Myc-dependent metabolic changes included higher levels of neutral lipid and acetyl-CoA in WT tumors. The latter correlated with higher histone H3 acetylation. Collectively, our results indicate that Myc's role in HB pathogenesis is to impose mutually dependent changes in gene expression and metabolic re-programming that are unattainable in non-transformed cells and that cooperate to maximize tumor growth.
Copyright ยฉ 2016, The American Society for Biochemistry and Molecular Biology. โข Keywords: Myc (c-Myc), Beta-catenin (B-catenin), Hepatocellular carcinoma, Metabolism, Yes-associated protein (YAP)
โข O2k-Network Lab: US PA Pittsburgh Goetzman ES
Labels: MiParea: Respiration, mtDNA;mt-genetics, Genetic knockout;overexpression
Pathology: Cancer
Organism: Mouse Tissue;cell: Liver Preparation: Homogenate Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase
Coupling state: LEAK, OXPHOS Pathway: N, S, NS HRR: Oxygraph-2k
2016-11, US