Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer
Abstract
Increasing evidence suggests that extracellular vesicles (EVs) can transfer genetic material to recipient cells. However, the mechanism and role of this phenomenon are largely unknown. Here we have made a remarkable discovery: EVs can harbor the full mitochondrial genome. These extracellular vesicles can in turn transfer their mtDNA to cells with impaired metabolism, leading to restoration of metabolic activity. We determined that hormonal therapy induces oxidative phosphorylation-deficient breast cancer cells, which can be rescued via the transfer of mtDNA-laden extracellular vesicles. Horizontal transfer of mtDNA occurred in cancer stem-like cells and was associated with increased self-renewal potential of these cells, leading to resistance to hormonal therapy. We propose that mtDNA transfer occurs in human cancer via EVs.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 11, 2017
- Source ID
- 10.1073/pnas.1704862114
Entities
People
- Alexander Galkin
- Anna Stepanova
- Antonio Strillacci
- Ayuko Hoshino
- Basant Kumar Thakur
- Chiara Mastroleo
- Claudia Savini
- David Lyden
- Giuseppe Gasparre
- Ivana Kurelac
- Jacqueline Bromberg
- Kunihiro Uryu
- Larry Norton
- Laura Benedetta Amato
- Laura Daly
- Luisa Iommarini
- Massimiliano Bonafé
- Monica Cricca
- Nadine Soplop
- Pasquale Sansone
- Qing Chang
Organizations
- Congressionally Directed Medical Research Programs
- Memorial Sloan Kettering Cancer Center
- National Institutes of Health
- Queen's University Belfast
- University of Bologna
- Weill Cornell Medicine