Cancer cells exploit adaptive mitochondrial dynamics to increase tumor cell invasion

Cell Cycle
M Cecilia Caino, Dario C Altieri

Abstract

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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Citations

Oct 13, 2018·Cancer Science·Long-Long XieYa Cao
Mar 7, 2018·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Ruizhi WangXiaolin Wang
May 21, 2020·Signal Transduction and Targeted Therapy·Longlong XieYa Cao
Jul 17, 2020·Cancer Reports·Madison Furnish, M Cecilia Caino
Nov 13, 2020·The FEBS Journal·Camila Castillo FerrerGabriel Ichim
Jul 29, 2019·Mitochondrion·Ashutosh Agrawal, Rajesh Ramachandran
Jan 26, 2021·Frontiers in Oncology·Lingling WangXiaochen Wang
May 22, 2020·Signal Transduction and Targeted Therapy·Longlong XieYa Cao

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Methods Mentioned

BETA
GTPases
environmental stress
protein folding
xenograft

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