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Control of Tumor Bioenergetics and Survival Stress Signaling by Mitochondrial HSP90s
- Source :
- Cancer Cell. 22(3):331-344
- Publication Year :
- 2012
- Publisher :
- Elsevier BV, 2012.
-
Abstract
- Tumors successfully adapt to constantly changing intra- and extra-cellular environments, but the wirings of this process are still largely elusive. Here, we show that Heat Shock Protein 90 (HSP90)-directed protein folding in mitochondria, but not cytosol, maintains energy production in tumor cells. Interference with this process activates a signaling network that involves phosphorylation of nutrient-sensing AMP-activated kinase (AMPK), inhibition of rapamycin-sensitive mTOR complex 1 (mTORC1), induction of autophagy, and expression of an endoplasmic reticulum (ER) unfolded protein response (UPR). This signaling network confers a survival and proliferative advantage to genetically disparate tumors, and correlates with worse outcome in lung cancer patients. Therefore, mitochondrial HSP90s are adaptive regulators of tumor bioenergetics, and tractable targets for cancer therapy.
- Subjects :
- Protein Folding
Cancer Research
Lung Neoplasms
Kinesins
mTORC1
Mitochondrion
AMP-Activated Protein Kinases
Endoplasmic Reticulum
Guanidines
Mice
0302 clinical medicine
Cytosol
AMP-Activated Protein Kinase Kinases
Neoplasms
Endoplasmic reticulum unfolded protein response
Phosphorylation
RNA, Small Interfering
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
0303 health sciences
TOR Serine-Threonine Kinases
Cell biology
Mitochondria
Oncology
030220 oncology & carcinogenesis
RNA Interference
Signal transduction
Signal Transduction
Cell Survival
Lactams, Macrocyclic
Biology
Mechanistic Target of Rapamycin Complex 1
Protein Serine-Threonine Kinases
Article
03 medical and health sciences
Heat shock protein
Cell Line, Tumor
Autophagy
Animals
Humans
HSP90 Heat-Shock Proteins
030304 developmental biology
Cell Proliferation
Endoplasmic reticulum
Proteins
Cell Biology
Multiprotein Complexes
Unfolded protein response
Unfolded Protein Response
Energy Metabolism
Subjects
Details
- ISSN :
- 15356108
- Volume :
- 22
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Cancer Cell
- Accession number :
- edsair.doi.dedup.....c5824c511da27864a990d7ec04b34e24
- Full Text :
- https://doi.org/10.1016/j.ccr.2012.07.015