| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2107021 | Cancer Cell | 2015 | 15 Pages |
•MYC represses YAP/TAZ-dependent transcription•MYC-dependent changes in mitochondrial dynamics inhibit YAP/TAZ•MYC activates AMPK downstream of changes in mitochondrial dynamics•Activation of AMPK disrupts the TEAD-YAP interaction in MYC-driven breast cancer
SummaryIn several developmental lineages, an increase in MYC expression drives the transition from quiescent stem cells to transit-amplifying cells. We show that MYC activates a stereotypic transcriptional program of genes involved in cell growth in mammary epithelial cells. This change in gene expression indirectly inhibits the YAP/TAZ co-activators, which maintain the clonogenic potential of these cells. We identify a phospholipase of the mitochondrial outer membrane, PLD6, as the mediator of MYC activity. MYC-dependent growth strains cellular energy resources and stimulates AMP-activated kinase (AMPK). PLD6 alters mitochondrial fusion and fission dynamics downstream of MYC. This change activates AMPK, which in turn inhibits YAP/TAZ. Mouse models and human pathological data show that MYC enhances AMPK and suppresses YAP/TAZ activity in mammary tumors.
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