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채영찬

Chae, Young Chan
Cancer Translational Research Lab.
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PI3K therapy reprograms mitochondrial trafficking to fuel tumor cell invasion

Author(s)
Caino, M. CeciliaGhosh, Jagadish C.Chae, Young ChanVaira, ValentinaRivadeneira, Dayana B.Faversani, AliceRampini, PaoloKossenkov, Andrew V.Aird, Katherine M.Zhang, RugangWebster, Marie R.Weeraratna, Ashani T.Bosari, SilvanoLanguino, Lucia R.Altieri, Dario C.
Issued Date
2015-07
DOI
10.1073/pnas.1500722112
URI
https://scholarworks.unist.ac.kr/handle/201301/21831
Fulltext
http://www.pnas.org/content/112/28/8638
Citation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.112, no.28, pp.8638 - 8643
Abstract
Molecular therapies are hallmarks of "personalized" medicine, but how tumors adapt to these agents is not well-understood. Here we show that small-molecule inhibitors of phosphatidylinositol 3-kinase (PI3K) currently in the clinic induce global transcriptional reprogramming in tumors, with activation of growth factor receptors, (re)phosphorylation of Akt and mammalian target of rapamycin (mTOR), and increased tumor cell motility and invasion. This response involves redistribution of energetically active mitochondria to the cortical cytoskeleton, where they support membrane dynamics, turnover of focal adhesion complexes, and random cell motility. Blocking oxidative phosphorylation prevents adaptive mitochondrial trafficking, impairs membrane dynamics, and suppresses tumor cell invasion. Therefore, "spatiotemporal" mitochondrial respiration adaptively induced by PI3K therapy fuels tumor cell invasion, and may provide an important antimetastatic target.
Publisher
NATL ACAD SCIENCES
ISSN
0027-8424
Keyword (Author)
mitochondriamolecular therapycytoskeletonPI3Kcell invasion
Keyword
CANCER-CELLSOXIDATIVE-PHOSPHORYLATIONMETASTASISMIGRATIONDYNAMICSINHIBITORSGLYCOLYSISPROGRESSIONMETABOLISMACTIVATION

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