scholarly journals Heat Induction of the Unphosphorylated Form of Hypoxia-inducible Factor-1α Is Dependent on Heat Shock Protein-90 Activity

2002 ◽  
Vol 277 (11) ◽  
pp. 9262-9267 ◽  
Author(s):  
Dörthe M. Katschinski ◽  
Lu Le ◽  
Daniel Heinrich ◽  
Klaus F. Wagner ◽  
Thomas Hofer ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Hypoxia Inducible Factor ◽  
Heat Shock Protein 90 ◽  
Heat Induction ◽  
Hypoxia Inducible Factor 1Α

Interaction of heat shock protein 90 with hypoxia inducible factor and signal transducer and activator of transcription in colon cancer

2019 ◽  
Vol 86 ◽  
pp. 151-158 ◽  
Author(s):  
Walid L. Shaib ◽  
Ganji Purnachandra Nagaraju ◽  
Batoul Farran ◽  
Gregory B. Lesinski ◽  
Bassel F. El-Rayes
Keyword(s):  
Colon Cancer ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Hypoxia Inducible Factor ◽  
Heat Shock Protein 90 ◽  
Signal Transducer

scholarly journals Induction of the Hypoxia-Inducible Factor System by Low Levels of Heat Shock Protein 90 Inhibitors

2005 ◽  
Vol 65 (23) ◽  
pp. 11094-11100 ◽  
Author(s):  
Nadia O. Ibrahim ◽  
Torsten Hahn ◽  
Corinna Franke ◽  
Daniel P. Stiehl ◽  
Renato Wirthner ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Hypoxia Inducible Factor ◽  
Heat Shock Protein 90 ◽  
Low Levels ◽  
Factor System

scholarly journals A potentially common peptide target in secreted heat shock protein-90α for hypoxia-inducible factor-1α–positive tumors

2012 ◽  
Vol 23 (4) ◽  
pp. 602-613 ◽  
Author(s):  
Divya Sahu ◽  
Zhengwei Zhao ◽  
Fred Tsen ◽  
Chieh-Fang Cheng ◽  
Ryan Park ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Hypoxia Inducible Factor ◽  
Metastatic Breast ◽  
Tumor Formation ◽  
Promoting Effect ◽  
Hypoxia Inducible Factor 1Α ◽  
Amino Acid Region ◽  
Lung Colonization

Deregulated accumulation of hypoxia-inducible factor-1α (HIF-1α) is a hallmark of many solid tumors. Directly targeting HIF-1α for therapeutics is challenging. Our finding that HIF-1α regulates secretion of heat shock protein-90α (Hsp90α) for cell migration raises the exciting possibility that targeting the secreted Hsp90α from HIF-1α–positive tumors has a better clinical outlook. Using the HIF-1α–positive and metastatic breast cancer cells MDA-MB-231, we show that down-regulation of the deregulated HIF-1α blocks Hsp90α secretion and invasion of the cells. Reintroducing an active, but not an inactive, HIF-1α into endogenous HIF-1α–depleted cells rescues both Hsp90α secretion and invasion. Inhibition of Hsp90α secretion, neutralization of secreted Hsp90α action, or removal of the cell surface LRP-1 receptor for secreted Hsp90α reduces the tumor cell invasion in vitro and lung colonization and tumor formation in nude mice. Furthermore, we localized the tumor-promoting effect to a 115–amino acid region in secreted Hsp90α called F-5. Supplementation with F-5 is sufficient to bypass the blockade of HIF-1α depletion and resumes invasion by the tumor cells under serum-free conditions. Because normal cells do not secrete Hsp90α in the absence of stress, drugs that target F-5 should be more effective and less toxic in treatment of HIF-1α–positive tumors in humans.

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