Dynamic regulation of mitochondrial pyruvate metabolism is necessary for orthotopic pancreatic tumor growth.
Nancy P Echeverri RuizVijay MohanJinghai WuSabina ScottMcKenzie KreamerMartin BenejTereza GoliasIoanna PapandreouNicholas C DenkoPublished in: Cancer & metabolism (2021)
We found that any substitution of alanine for serine at regulatory sites generated a hypomorphic PDC. However, the reduced PDC activity was insensitive to further reduction in hypoxia. These cells had a very modest reduction of growth in vitro, but failed to grow as tumors indicating that dynamic PDC adaptation to microenvironmental conditions is necessary to support pancreatic cancer growth in vivo.