title: Cancer cells exploit adaptive mitochondrial dynamics to increase tumor cell invasion.
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.
authors: a Prostate Cancer Discovery and Development Program, Tumor Microenvironment and Metastasis Program, The Wistar Institute ; Philadelphia , PA USA.
authors: M Cecilia
authors: MC
authors: Caino
authors: a Prostate Cancer Discovery and Development Program, Tumor Microenvironment and Metastasis Program, The Wistar Institute ; Philadelphia , PA USA.
authors: Dario C
authors: DC
authors: Altieri
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D063154:Mitochondrial Dynamics / Q000187:drug effects / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt
keywords: Hsp90; PI3K; drug resistance; focal adhesion; metastasis; mitochondria