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  Ca2+  sensitive  Calcineurin  (Ppp3ca)  and  the expression  of
   PI3-kinase  (Pik3r4  and  Pik3cb)  increased  by  two folds.   This
   Ca2+/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 or more 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 0.00001).  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.

   (Genomics Data, doi:10.1016/j.gdata.2015.07.031, 2015)