Figures & data
Figure 1. PI3K repositions mitochondria to increase tumor cell invasion. In this schematic representation, tumor cells are drawn based on representative cellular morphology and actual mitochondrial localization. Mitochondria are green, cytoskeleton is blue and the nucleus is red. Top, Treatment of tumor cells with PI3K inhibitors used in the clinic initiates a compensatory adaptive response centered on reactivation of Akt2 and mTOR. As a result, mitochondria travel to the cortical cytoskeleton, a process that requires elongation (Mitofusin1) and active mitochondrial respiration (OxPhos). Bottom, Rewired cells juxtapose mitochondria to focal adhesions (FA), where they provide a regional source of energy and accelerate focal adhesion dynamics. The mitochondrial Hsp90 chaperones overcome metabolic stress and maintain OxPhos by folding complex II. A mitochondrially-targeted Hsp90 inhibitor, Gamitrinib, prevents PI3Ki-induced pro-invasive responses.
