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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 05, 2015 |
| Title |
Disruption of Cytochrome c Oxidase Function Induces Warburg Effect and Metabolic Reprogramming |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Defects in mitochondrial oxidative phosphorylation complexes, altered bioenergetics and metabolic shift are often seen in cancers. Here we show a role for the dysfunction of electron transport chain component, cytochrome c oxidase (CcO) in cancer progression. We show that genetic silencing of the CcO complex by shRNA expression and loss of CcO activity in multiple cell types from the mouse and human sources resulted in metabolic shift to glycolysis, loss of anchorage dependent growth and acquired invasive phenotypes. Disruption of CcO complex caused loss of transmembrane potential and induction of Ca2+/Calcineurin-mediated retrograde signaling. Propagation of this signaling, includes activation of PI3-kinase, IGF1R and Akt, Ca2+ sensitive transcription factors and also, TGF1, MMP16, periostin that are involved in oncogenic progression. Whole genome expression analysis showed up regulation of genes involved in cell signaling, extracellular matrix interactions, cell morphogenesis, cell motility and migration. The transcription profiles reveal extensive similarity to retrograde signaling initiated by partial mtDNA depletion, though distinct differences are observed in signaling induced by CcO dysfunction. The possible CcO dysfunction as a biomarker for cancer progression was supported by data showing that esophageal tumors from human patients show reduced CcO subunits IVi1 and Vb in regions that were previously shown to be hypoxic core of the tumors. Our results show that mitochondrial electron transport chain defect initiates a retrograde signaling. These results suggest that a defect in CcO complex can potentially induce tumor progression.
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| Overall design |
Total RNA from control and CcO IVi1 silenced cells was extract. Three independent samples were generated for control and silenced, respectively.
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| Web link |
http://code.vet.upenn.edu/download/CcOdefect/
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| Contributor(s) |
Srinivasan S, Guha M, Dong DW, Whelan KA, Ruthel G, Uchikado Y, Natsugoe S, Nakagawa H, Avadhani NG |
| Citation(s) |
26148236 |
| Submission date |
May 04, 2015 |
| Last update date |
Feb 21, 2018 |
| Contact name |
Dawei W Dong |
| E-mail(s) |
ddong@mail.med.upenn.edu
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| Organization name |
University of Pennsylvania
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| Department |
Biomedical Sciences
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| Lab |
122B Anatomy–Chemistry Building
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| Street address |
3620 Hamilton Walk
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| City |
Philadelphia |
| State/province |
Pennsylvania |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA282975 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE68525_RAW.tar |
60.0 Mb |
(http)(custom) |
TAR (of CEL) |
| GSE68525_rma-gene-full.summary.txt.gz |
526.4 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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