PI3K therapy reprograms mitochondrial trafficking to fuel tumor cell invasion
Abstract
Despite the promise of personalized cancer medicine, most molecular therapies produce only modest and short-lived patient gains. In addition to drug resistance, it is also possible that tumors adaptively reprogram their signaling pathways to evade therapy-induced “stress” and, in the process, acquire more aggressive disease traits. We show here that small-molecule inhibitors of PI3K, a cancer node and important therapeutic target, induce transcriptional and signaling reprogramming in tumors. This involves the trafficking of energetically active mitochondria to subcellular sites of cell motility, where they provide a potent, “regional” energy source to support tumor cell invasion. Although this response may paradoxically increase the risk of metastasis during PI3K therapy, targeting mitochondrial reprogramming is feasible, and could provide a novel therapeutic strategy.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 29, 2015
- Source ID
- 10.1073/pnas.1500722112
Entities
People
- Alice Faversani
- Andrew V Kossenkov
- Ashani T. Weeraratna
- Dario C Altieri
- Dayana B. Rivadeneira
- Jagadish C. Ghosh
- Katherine M Aird
- Lucia R. Languino
- M Cecilia Caino
- Marie R. Webster
- Paolo Rampini
- Rugang Zhang
- Silvano Bosari
- Valentina Vaira
- Young Chan Chae
Organizations
- Milan Polyclinic
- National Institutes of Health
- Office of the Secretary of Defense
- Thomas Jefferson University
- University of Milan
- Wistar Institute