Targeting Heat Shock Protein 90 for the Treatment of Malignant Pheochromocytoma

Giubellino, Alessio; Sourbier, Carole; Lee, Min Jung; Scroggins, Brad; Bullova, Petra; Landau, Michael S.; Ying, Weiwen; Neckers, Len; Trepel, Jane B.; Pacák, Karel

doi:10.1371/journal.pone.0056083

Cited by 25 publications

(25 citation statements)

References 49 publications

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“…17-AAG (a derivative of the antibiotic geldanamycin) is a potent Hsp90 inhibitor that specifically binds to Hsp90's ATP-binding site and modulates its function (Whitesell et al, 1994; Prodromou et al, 1997; Pratt and Toft, 2003; Giubellino et al, 2013). The binding of these drugs to HSP90 facilitates the dissociation and activation of HSF1, which forms a complex with HSP90 in the resting cells (Figs.…”

Section: Hsp70 and Rgc Survivalmentioning

confidence: 99%

Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival

Piri

Kwong

et al. 2016

Progress in Retinal and Eye Research

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Heat shock proteins (HSPs) belong to a superfamily of stress proteins that are critical constituents of a complex defense mechanism that enhances cell survival under adverse environmental conditions. Cell protective roles of HSPs are related to their chaperone functions, antiapoptotic and antinecrotic effects. HSPs' antiapoptotic and cytoprotective characteristics, their ability to protect cells from a variety of stressful stimuli, and the possibility of their pharmacological induction in cells under pathological stress make these proteins an attractive therapeutic target for various neurodegenerative diseases; these include Alzheimer's, Parkinson's, Huntington's, prion disease, and others. This review discusses the possible roles of HSPs, particularly HSP70 and small HSPs (alpha A and alpha B crystallins) in enhancing the survival of retinal ganglion cells (RGCs) in optic neuropathies such as glaucoma, which is characterized by progressive loss of vision caused by degeneration of RGCs and their axons in the optic nerve. Studies in animal models of RGC degeneration induced by ocular hypertension, optic nerve crush and axotomy show that upregulation of HSP70 expression by hyperthermia, zinc, geranyl-geranyl acetone, 17-AAG (a HSP90 inhibitor), or through transfection of retinal cells with AAV2-HSP70 effectively supports the survival of injured RGCs. RGCs survival was also stimulated by overexpression of alpha A and alpha B crystallins. These findings provide support for translating the HSP70- and alpha crystallin-based cell survival strategy into therapy to protect and rescue injured RGCs from degeneration associated with glaucomatous and other optic neuropathies.

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Section: Hsp70 and Rgc Survivalmentioning

confidence: 99%

Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival

Piri

Kwong

et al. 2016

Progress in Retinal and Eye Research

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“…Thus, inhibitors of HSP90, such as geldanamycin and analogues like 17-allylaminogeldanamycin (17-AAG; tanespimycin), 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG; alespimicin), or other new analogues, are promising therapeutic agents (Isaacs, et al 2002; Northcott, et al 2012). Giubelino et al (Giubellino, et al 2013) demonstrated potent inhibition of proliferation and migration of PHEO cell lines and induced degradation of key Hsp90 clients by 17-AAG and ganetespib. They also showed the efficacy of 17-AAG and ganetespib in reducing metastatic burden and increasing survival in metastatic model of PHEO (Giubellino et al 2013).…”

Section: Future Treatment Options To Attack Metabolic Alterations In mentioning

confidence: 99%

“…Giubelino et al (Giubellino, et al 2013) demonstrated potent inhibition of proliferation and migration of PHEO cell lines and induced degradation of key Hsp90 clients by 17-AAG and ganetespib. They also showed the efficacy of 17-AAG and ganetespib in reducing metastatic burden and increasing survival in metastatic model of PHEO (Giubellino et al 2013). …”

Section: Future Treatment Options To Attack Metabolic Alterations In mentioning

confidence: 99%

Current views on cell metabolism in SDHx-related pheochromocytoma and paraganglioma

Vícha¹,

Taïeb²,

Pacák³

2014

Endocrine-Related Cancer

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Warburg’s metabolic hypothesis is based on the assumption that a cancer cell’s respiration must be under attack, leading to its damage, in order to obtain increased glycolysis. Although this may not apply to all cancers, there is some evidence proving that primarily abnormally functioning mitochondrial complexes are indeed related to cancer development. Thus, mutations in complex II (succinate dehydrogenase (SDH)) lead to the formation of pheochromocytoma/paraganglioma. Mutations in one of the SDH genes (SDHx mutations) lead to succinate accumulation associated with very low fumarate levels, increased glutaminolysis, the generation of reactive oxygen species (ROS), and pseudohypoxia. This results in significant changes in signaling pathways (many of them dependent on the stabilization of hypoxia-inducible factor (HIF)) including oxidative phosphorylation, glycolysis, specific expression profiles, as well as genomic instability and increased mutability resulting in tumor development. Although there is currently no very effective therapy for SDHx-related metastatic pheochromocytomas/paragangliomas, targeting their fundamental metabolic abnormalities may provide a unique opportunity for the development of novel and more effective forms of therapy for these tumors.

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“…The role of ERK-1/2 MAPK-signaling pathway and HSP90 in CXCL1 inhibition of ASMC migration ASMCs were treated for 1 h at 37˚C with either ERK-1/2 MAPK inhibitor PD184352 (2 mM; US Biological, Swampscott, MA) (34) or with different concentrations (1, 10, or 100 nM) of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), a low-toxicity profile pan inhibitor of HSP90 (35) (AG Scientific, San Diego, CA) prior to the addition of CXCL1 to the Boyden chamber. Controls were exposed to the same concentration of DMSO.…”

Section: Migration Assaymentioning

confidence: 99%

CXCL1 Inhibits Airway Smooth Muscle Cell Migration through the Decoy Receptor Duffy Antigen Receptor for Chemokines

Al-Alwan

Chang

Rousseau

et al. 2014

The Journal of Immunology

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Airway smooth muscle cell (ASMC) migration is an important mechanism postulated to play a role in airway remodeling in asthma. CXCL1 chemokine has been linked to tissue growth and metastasis. In this study, we present a detailed examination of the inhibitory effect of CXCL1 on human primary ASMC migration and the role of the decoy receptor, Duffy AgR for chemokines (DARC), in this inhibition. Western blots and pathway inhibitors showed that this phenomenon was mediated by activation of the ERK-1/2 MAPK pathway, but not p38 MAPK or PI3K, suggesting a biased selection in the signaling mechanism. Despite being known as a nonsignaling receptor, small interference RNA knockdown of DARC showed that ERK-1/2 MAPK activation was significantly dependent on DARC functionality, which, in turn, was dependent on the presence of heat shock protein 90 subunit α. Interestingly, DARC- or heat shock protein 90 subunit α–deficient ASMCs responded to CXCL1 stimulation by enhancing p38 MAPK activation and ASMC migration through the CXCR2 receptor. In conclusion, we demonstrated DARC’s ability to facilitate CXCL1 inhibition of ASMC migration through modulation of the ERK-1/2 MAPK–signaling pathway.

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Targeting Heat Shock Protein 90 for the Treatment of Malignant Pheochromocytoma

Cited by 25 publications

References 49 publications

Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival

Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival

Current views on cell metabolism in SDHx-related pheochromocytoma and paraganglioma

CXCL1 Inhibits Airway Smooth Muscle Cell Migration through the Decoy Receptor Duffy Antigen Receptor for Chemokines

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