Journal
CELL CYCLE
Volume 14, Issue 20, Pages 3242-3247Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15384101.2015.1084448
Keywords
drug resistance; focal adhesion; Hsp90; mitochondria; metastasis; PI3K
Categories
Funding
- National Institutes of Health (NIH) [P01 CA140043, R01 CA78810, CA190027, F32CA177018]
- Prostate Cancer Foundation
- Office of the Assistant Secretary of Defense for Health Affairs through the Prostate Cancer Research Program [W81XWH-13-1-0193]
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Mitochondria are organelles that orchestrate a plethora of fundamental cellular functions that have been associated with various steps of tumor progression. However, we currently lack a mechanistic understanding of how mitochondrial dynamics, which reflects the organelles' exquisite heterogeneity in shape and spatial distribution, affects tumorigenesis. In a recent study, we uncovered a surprising new role of mitochondrial dynamics in response to PI3K therapy. We found that re-activation of Akt/mTOR signaling in tumor cells exposed to small molecule PI3K antagonists currently in the clinic triggered the transport of energetically active, elongated mitochondria to the cortical cytoskeleton of tumor cells. In turn, these repositioned mitochondria supported increased lamellipodia dynamics, faster turnover of focal adhesion complexes, heightened velocity and distance of random cell migration and increased tumor cell invasion. In this Extra View, we discuss the mechanistic basis of this paradoxical response to PI3K antagonists and propose possible strategies to disable mitochondrial adaptation.
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