| Literature DB >> 26678338 |
Björn von Eyss1, Laura A Jaenicke1, Roderik M Kortlever2, Nadine Royla3, Katrin E Wiese1, Sebastian Letschert4, Leigh-Anne McDuffus5, Markus Sauer4, Andreas Rosenwald6, Gerard I Evan2, Stefan Kempa3, Martin Eilers7.
Abstract
In 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.Entities:
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Year: 2015 PMID： 26678338 DOI： 10.1016/j.ccell.2015.10.013
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743