PMID- 26697345
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20151223
LR  - 20201001
IS  - 2213-5960 (Print)
IS  - 2213-5960 (Electronic)
IS  - 2213-5960 (Linking)
VI  - 6
DP  - 2015 Dec
TI  - Defects in cytochrome c oxidase expression induce a metabolic shift to glycolysis 
      and carcinogenesis.
PG  - 99-107
LID - 10.1016/j.gdata.2015.07.031 [doi]
AB  - Mitochondrial metabolic dysfunction is often seen in cancers. This paper shows 
      that the defect in a mitochondrial electron transport component, the cytochrome c 
      oxidase (CcO), leads to increased glycolysis and carcinogenesis. Using whole 
      genome microarray expression analysis we show that genetic silencing of the CcO 
      subunit Cox4i1 in mouse C2C12 myoblasts resulted in metabolic shift to 
      glycolysis, activated a retrograde stress signaling, and induced carcinogenesis. 
      In the knockdown cells, the expression of Cox4i1 was less than 5% of the control 
      and the expression of the irreversible glycolytic enzymes (Hk1, Pfkm and Pkm) 
      increased two folds, facilitating metabolic shift to glycolysis. The expression 
      of Ca (2+) sensitive Calcineurin (Ppp3ca) and the expression of PI3-kinase 
      (Pik3r4 and Pik3cb) increased by two folds. This Ca (2+)/Calcineurin/PI3K 
      retrograde stress signaling induced the up-regulation of many nuclear genes 
      involved in tumor progression. Overall, we found 1047 genes with 2-folds 
      expression change (with p-value less than 0.01) between the knockdown and the 
      control, among which were 35 up-regulated genes in pathways in cancer (enrichment 
      p-value less than 10(- 5)). Functional analysis revealed that the up-regulated 
      genes in pathways in cancer were dominated by genes in signal transduction, 
      regulation of transcription and PI3K signaling pathway. These results suggest 
      that a defect in CcO complex initiates a retrograde signaling which can induce 
      tumor progression. Physiological studies of these cells and esophageal tumors 
      from human patients support these results. GEO accession number = GSE68525.
FAU - Dong, Dawei W
AU  - Dong DW
AD  - The Department of Biomedical Sciences, School of Veterinary Medicines, University 
      of Pennsylvania, PA, United States ; Institute for Biomedical Informatics, 
      Perelman School of Medicine, University of Pennsylvania, PA, United States.
FAU - Srinivasan, Satish
AU  - Srinivasan S
AD  - The Department of Biomedical Sciences, School of Veterinary Medicines, University 
      of Pennsylvania, PA, United States.
FAU - Guha, Manti
AU  - Guha M
AD  - The Department of Biomedical Sciences, School of Veterinary Medicines, University 
      of Pennsylvania, PA, United States.
FAU - Avadhani, Narayan G
AU  - Avadhani NG
AD  - The Department of Biomedical Sciences, School of Veterinary Medicines, University 
      of Pennsylvania, PA, United States.
LA  - eng
GR  - R01 GM034883/GM/NIGMS NIH HHS/United States
GR  - R01 AR067066/AR/NIAMS NIH HHS/United States
GR  - P30 DK050306/DK/NIDDK NIH HHS/United States
GR  - R01 CA022762/CA/NCI NIH HHS/United States
GR  - R37 CA022762/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20150814
PL  - United States
TA  - Genom Data
JT  - Genomics data
JID - 101634120
PMC - PMC4664720
OTO - NOTNLM
OT  - Cytochrome c oxidase defects
OT  - Functional analysis
OT  - Genome expression
OT  - Mitochondrial metabolic dysfunction
OT  - Tumor progression
EDAT- 2015/12/24 06:00
MHDA- 2015/12/24 06:01
PMCR- 2015/08/14
CRDT- 2015/12/24 06:00
PHST- 2015/06/29 00:00 [received]
PHST- 2015/07/19 00:00 [revised]
PHST- 2015/07/26 00:00 [accepted]
PHST- 2015/12/24 06:00 [entrez]
PHST- 2015/12/24 06:00 [pubmed]
PHST- 2015/12/24 06:01 [medline]
PHST- 2015/08/14 00:00 [pmc-release]
AID - S2213-5960(15)00180-4 [pii]
AID - 10.1016/j.gdata.2015.07.031 [doi]
PST - epublish
SO  - Genom Data. 2015 Aug 14;6:99-107. doi: 10.1016/j.gdata.2015.07.031. eCollection 
      2015 Dec.