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| Status |
Public on Jan 24, 2020 |
| Title |
Oxidative phosphorylation promotes primary melanoma invasion |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Dermal invasion is a hallmark of malignant melanoma. The molecular alterations driving the progression of primary melanoma to metastatic disease have been studied extensively, whereas the early progression of non-invasive primary melanoma to an invasive state is not well understood. To elucidate the mechanisms underlying the transition from radial to vertical growth, the first step in melanoma invasion, we developed a zebrafish melanoma model in which constitutive activation of ribosomal protein S6 kinase 1 (RSK1) drives tumor invasion. Transcriptomic analysis of RSK1-activated tumors identified metabolic changes, including upregulation of genes associated with oxidative phosphorylation. Vertical growth phase human melanoma cells show higher oxygen consumption and preferential utilization of glutamine compared to radial growth phase melanoma cells. Peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1a has been proposed as a master regulator of tumor oxidative phosphorylation. In human primary melanoma specimens we show that PGC1a protein expression is positively associated with increased tumor thickness and expression of the proliferative marker Ki-67 and the reactive oxygen species (ROS) scavenger SCARA3. PGC1a depletion modulates cellular processes associated with primary melanoma growth and invasion, including oxidative stress. Our results support a role for PGC1a in mediating glutamine-driven OXPHOS to facilitate the invasive growth of primary melanoma.
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| Overall design |
Melanomas harvested from MiniCoopR-GFP zebrafish (n=6) and MiniCoopR-myrRSK (n=6) zebrafish
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| Contributor(s) |
Osman I, Houvras Y |
| Citation(s) |
32142731 |
| Submission date |
Jan 23, 2020 |
| Last update date |
Apr 28, 2020 |
| Contact name |
Yariv Houvras |
| Organization name |
Weill Cornell Medical College
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| Department |
Surgery
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| Street address |
1300 York Ave
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL14875 |
Illumina HiSeq 2000 (Danio rerio) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA602818 |
| SRA |
SRP244262 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE144117_diff_exp_deseq2.csv.gz |
3.9 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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