|
| Status |
Public on Oct 28, 2016 |
| Title |
Coordinated Activities of Multiple Myc-Dependent and Myc-Independent Biosynthetic Pathways in Hepatoblastoma |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Hepatoblastoma (HB) is associated with aberrant activation of the b-catenin and Hippo/YAP signaling pathways. Over-expression of mutant b-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 b-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.
|
| |
|
| Overall design |
4 individual sets each of Myc WT and KO hepatocytes, and 5 individual sets each of Myc WT and KO Hepatoblastoma
|
| |
|
| Contributor(s) |
Prochownik EV, Wang H |
| Citation(s) |
27738108 |
| |
| Submission date |
Oct 03, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Edward V Prochownik |
| E-mail(s) |
edward.prochownik@chp.edu
|
| Phone |
412-692-6795
|
| Organization name |
Children’s Hospital of Pittsburgh of UPMC
|
| Department |
Division of Hematology/Oncology
|
| Street address |
4401 Penn Ave.
|
| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15224 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
|
| Samples (18)
|
|
| Relations |
| BioProject |
PRJNA345228 |
| SRA |
SRP090770 |
Less...
More...