期刊
ONCOTARGET
卷 5, 期 23, 页码 11897-11908出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.2472
关键词
TRAP1; mitochondria; chaperones; cancer metabolism; ROS; succinate dehydrogenase
资金
- PRIN/MIUR [RBAP11S8C3, RBLA03S4SP]
- FIRB/MIUR [RBAP11S8C3, RBLA03S4SP]
- Progetti di Ateneo [CPDA123598]
- Progetti Strategici dell'Universita di Padova
- Associazione Italiana per la Ricerca sul Cancro [8722, 13392]
TRAP1 is a mitochondrial chaperone highly expressed in many tumor types; it inhibits respiratory complex II, down-modulating its succinate dehydrogenase (SDH) enzymatic activity. SDH inhibition in turn leads to a pseudohypoxic state caused by succinate-dependent HIF1 alpha stabilization and promotes neoplastic growth. Here we report that TRAP1 inhibition of SDH also shields cells from oxidative insults and from the ensuing lethal opening of the mitochondrial permeability transition pore. This anti-oxidant activity of TRAP1 protects tumor cells from death in conditions of nutrient paucity that mimic those encountered in the neoplasm during the process of malignant accrual, and it is required for in vitro tumorigenic growth. Our findings demonstrate that SDH inhibition by TRAP1 is oncogenic not only by inducing pseudohypoxia, but also by protecting tumor cells from oxidative stress.
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