Differential Expression of Mitochondrial Biogenesis Markers in Mouse and Human SHH-Subtype Medulloblastoma

Cells. 2019 Mar 5;8(3):216. doi: 10.3390/cells8030216.

Abstract

Medulloblastoma is a brain tumor that arises predominantly in infants and children. It is the most common pediatric brain malignancy. Around 25% of medulloblastomas are driven by constitutive activation of the Hedgehog signaling pathway. Hedgehog-driven medulloblastoma is often studied in the laboratory using genetic mouse models with overactive Hedgehog signaling, which recapitulate many of the pathological features of human Hedgehog-dependent tumors. However, we show here that on a molecular level the human and mouse HH-dependent MB are quite distinct, with human, but not mouse, tumors characterized by the presence of markers of increased oxidative phosphorylation and mitochondrial biogenesis. The latter suggests that, unlike for many other types of tumors, a switch to glycolytic metabolism might not be co-opted by human SHH-MB to perpetuate their survival and growth. This needs to be taken into consideration and could potentially be exploited in the design of therapies.

Keywords: Shh; Sonic hedgehog; Warburg effect; gene expression; glycolysis; medulloblastoma; mitochondria; mouse model; oxidative phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Electron Transport Complex IV / metabolism
  • Gene Expression Regulation, Neoplastic
  • Hedgehog Proteins / metabolism*
  • Humans
  • Medulloblastoma / genetics
  • Medulloblastoma / metabolism*
  • Mice
  • Mitochondria / metabolism
  • Neoplasm Proteins / metabolism
  • Organelle Biogenesis*
  • Oxidative Phosphorylation
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Hedgehog Proteins
  • Neoplasm Proteins
  • SHH protein, human
  • Shh protein, mouse
  • Tumor Suppressor Protein p53
  • Electron Transport Complex IV