A MYC-driven change in mitochondrial dynamics limits YAP/TAZ function in mammary epithelial cells and breast cancer

Item Type:	Article
Title:	A MYC-driven change in mitochondrial dynamics limits YAP/TAZ function in mammary epithelial cells and breast cancer
Creators Name:	von Eyss, B. and Jaenicke, L.A. and Kortlever, R.M. and Royla, N. and Wiese, K.E. and Letschert, S. and McDuffus, L.A. and Sauer, M. and Rosenwald, A. and Evan, G.I. and Kempa, S. and Eilers, M.
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.
Keywords:	AMP-Activated Protein Kinases, Breast Neoplasms, Cell Line, Cell Lineage, Computational Biology, Enzyme Activation, Enzyme Induction, Epithelial Cells, Gene Expression Profiling, Genetic Databases, Human Mammary Glands, Mitochondria, Mitochondrial Dynamics, Neoplastic Gene Expression Regulation, Phenotype, Phospholipase D, Phosphoproteins, Phosphorylation, Proto-Oncogene Proteins c-myc, RNA Interference, Signal Transducing Adaptor Proteins, Signal Transduction, Time Factors, Transcription Factors, Transfection, Transgenic Mice, Animals, Mice
Source:	Cancer Cell
ISSN:	1535-6108
Publisher:	Cell Press / Elsevier
Volume:	28
Number:	6
Page Range:	743-757
Date:	14 December 2015
Official Publication:	https://doi.org/10.1016/j.ccell.2015.10.013
PubMed:	View item in PubMed

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