Control of Tumor Bioenergetics and Survival Stress Signaling by Mitochondrial HSP90s

Young Chan Chae, M. Cecilia Caino, Sofia Lisanti, Jagadish C. Ghosh, Takehiko Dohi, Nika N. Danial, Jessie Villanueva, Stefano Ferrero, Valentina Vaira, Luigi Santambrogio, Silvano Bosari, Lucia R. Languino, Meenhard Herlyn, Dario C. Altieri

Research output: Contribution to journalArticlepeer-review

Abstract

Tumors successfully adapt to constantly changing intra- and extracellular environments, but the wirings of this process are still largely elusive. Here, we show that heat-shock-protein-90-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, inhibition of rapamycin-sensitive mTOR complex 1, induction of autophagy, and expression of an endoplasmic reticulum unfolded protein response. This signaling network confers a survival and proliferative advantage to genetically disparate tumors, and correlates with worse outcome in lung cancer patients. Therefore, mitochondrial heat shock protein 90s are adaptive regulators of tumor bioenergetics and tractable targets for cancer therapy.

Original languageEnglish
Pages (from-to)331-344
Number of pages14
JournalCancer Cell
Volume22
Issue number3
DOIs
Publication statusPublished - Sep 11 2012

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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