Targeting Heat Shock Proteins in Cancer: A Promising Therapeutic Approach

Chatterjee, Suman; Burns, Timothy F.

doi:10.3390/ijms18091978

Cited by 413 publications

(317 citation statements)

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“…This role is clearly exposed when we describe both kinases and STAT proteins as HSP90 client proteins. The current literature points to the important role of HSP90/STAT3/STAT5 in cancer growth and the ability to thwart chemotherapy [3,[196][197][198].…”

Section: Discussionmentioning

confidence: 99%

Chaperoning STAT3/5 by Heat Shock Proteins: Interest of Their Targeting in Cancer Therapy

Hermetet

Girodon

Jego

2019

Cancers

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While cells from multicellular organisms are dependent upon exogenous signals for their survival, growth, and proliferation, commitment to a specific cell fate requires the correct folding and maturation of proteins, as well as the degradation of misfolded or aggregated proteins within the cell. This general control of protein quality involves the expression and the activity of molecular chaperones such as heat shock proteins (HSPs). HSPs, through their interaction with the STAT3/STAT5 transcription factor pathway, can be crucial both for the tumorigenic properties of cancer cells (cell proliferation, survival) and for the microenvironmental immune cell compartment (differentiation, activation, cytokine secretion) that contributes to immunosuppression, which, in turn, potentially promotes tumor progression. Understanding the contribution of chaperones such as HSP27, HSP70, HSP90, and HSP110 to the STAT3/5 signaling pathway has raised the possibility of targeting such HSPs to specifically restrain STAT3/5 oncogenic functions. In this review, we present how HSPs control STAT3 and STAT5 activation, and vice versa, how the STAT signaling pathways modulate HSP expression. We also discuss whether targeting HSPs is a valid therapeutic option and which HSP would be the best candidate for such a strategy.

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Section: Discussionmentioning

confidence: 99%

Chaperoning STAT3/5 by Heat Shock Proteins: Interest of Their Targeting in Cancer Therapy

Hermetet

Girodon

Jego

2019

Cancers

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“…The inability of 17-AAG to protect SH-SY5Y cells from proteasome stress observed in our experiments might be explained by lower extent of Hsp70 induction after pretreatment of the cells with 17-AAG as compared to the levels of Hsp70 induced by CoCl 2 . On contrary, despite induction of protective Hsp70 17-AAG exhibits also cytotoxic effects and was tested for treatment of different cancers (Chatterjee and Burns 2017). Although, we did not incubate cells simultaneously with 17-AAG and bortezomib, it is important to note that combination of 17-AAG with bortezomib was associated with synergistic cell death effect on U266 (Duus et al 2006) and MCF-7 (Mimnaugh et al 2004)…”

Section: Discussionmentioning

confidence: 97%

Cobalt chloride affects the death of SH-SY5Y cells induced by inhibition of ubiquitin proteasome system. Role of heat shock protein 70 and caspase 3

Saksonova

Brodňanová²,

Dibdiaková³

et al. 2018

gpb

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The aim our study was to investigate protective effect of cobalt chloride (CoCl 2 ) in the model of proteasome stress of neuroblastoma SH-SY5Y cells induced by bortezomib, an inhibitor of 26S proteasome. We have focused our interests on Hsp70 and activation of caspase 3. Finally, we have compared the effect of CoCl 2 with an effect of the pre-treatment of the cells with 17-AAG, an inhibitor of Hsp90 that is capable to induce expression of Hsp70, or with IOX2, an inhibitor of isoform 2 of prolyl hydroxylase that increases stability of hypoxia-inducible factor 1α (HIF1α). Pre-treatment of SH-SY5Y cells for 24 h with CoCl 2 , at concentrations of 150 or 250 µmol/l, and with 17-AAG at concentration 1 µmol/l but not with IOX2 at concentration 100 µmol/l, was associated with significantly increased expression of Hsp70. We have shown that pre-treatment of SH-SY5Y cells with CoCl 2 but not with 17-AAG or IOX2 was associated with significant delay of the cell death induced by proteasome stress. CoCl 2 -mediated effect was consistent with inhibition of bortezomib-induced caspase 3 activation in the cells pre-treated with CoCl 2 . Despite established neuroprotective properties of Hsp70 our results do not provide strong evidence that the effect of CoCl 2 could be mainly attributed to the ability of CoCl 2 to induce expression of Hsp70 and other mechanisms have to be considered.

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“…Examining all HSPs identified in this study, we found that 20 HSPs were identified in spermathecae overall and only 13 were identified in the semen (Fig 6); however, the precise functions of specific honey bee HSPs are largely unknown. By contrast, mammalian HSPs have been studied extensively; research on human sHSPs has focused on their roles in many types of cancer (osteosarcoma, leukemia, breast, colorectal, hepatic, gastric, and prostate cancer) 59,60 , where their upregulation is associated with both pro-and anti-apoptotic properties and mitigating ROS production 54,57,61,62 .…”

Section: Figure 3 Heat-shock Does Not Affect Expression Of Superoxidmentioning

confidence: 99%

Honey bee queens are vulnerable to heat-induced loss of fertility

McAfee

Chapman

Higo

et al. 2019

Preprint

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13All species need to reproduce to maintain viable populations, but heat stress kills sperm cells across the 14 animal kingdom and rising frequencies of heatwaves are a threat to biodiversity. Honey bees (Apis 15 mellifera) are globally distributed micro-livestock; therefore, they could serve as environmental 16 biomonitors for heat-induced reductions in fertility. Here, we found that queens have two potential 17 routes of temperature-stress exposure: within colonies and during routine shipping. Our data suggest 18 that temperatures of 15 to 38°C are safe for queens at a tolerance threshold of 11.5% loss of sperm 19 viability, which is the viability difference between failed and healthy queens collected from beekeepers. 20Heat shock activates expression of specific ATP-independent heat-shock proteins in the spermatheca, 21 which could serve as biomarkers for heat stress. This protein fingerprint may eventually enable surveys 22 with colony losses 41 . Furthermore, internal hive temperatures positively correlate with ambient 46 temperatures above 18°C, and brood nest temperatures can rise upwards of 37°C, both under natural 47 conditions 42 and during simulated heatwaves 43 . Hives occasionally experience spikes of > 40°C 44 , 48 suggesting that queens could be vulnerable to temperature extremes even inside the hive. 49Honey bees have excellent potential for being temperature stress biomonitors. They are a globally 50 distributed, managed species, so they are readily available in almost any geographic region, and they are 51 already accepted as effective biomonitors for pollution 45 . If we begin to observe signs of heat stress in 52 honey bees colonies, that would signal a worrisome risk of reduced reproductive output for ectothermic 53 species. 54Here, we begin to explore honey bees' utility as temperature stress biomonitors. We monitored 55 temperature fluctuations in colonies under extreme weather conditions, establishing that damaging 56 intra-hive temperatures can occur. Next, we tested a range of temperatures and exposure durations to 57 determine thresholds above which queen quality is likely to be compromised. We then investigated the 58 biochemical basis of heat-induced sperm viability reduction in queens and drones using quantitative 59 proteomics, which showed how heat stress alters protein expression of reproductive tissues. The 60 specific set of upregulated proteins we identified may eventually serve as diagnostic tools to elucidate 61 causes of queen failure and eventually enable regional surveys of heat stress as part of an 62 environmental temperature biomonitoring program. 63 Results and Discussion 64 Stored sperm viability of failed and healthy queens 65To establish how much of a reduction in sperm viability is associated with field-observable reduced 66 reproductive output (and associated economic losses for beekeepers), we collected queens rated as 67 'failing' (N = 58) and 'healthy' (N = 55) by beekeepers and measured the queens' stored sperm viability 68

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Targeting Heat Shock Proteins in Cancer: A Promising Therapeutic Approach

Cited by 413 publications

References 294 publications

Chaperoning STAT3/5 by Heat Shock Proteins: Interest of Their Targeting in Cancer Therapy

Chaperoning STAT3/5 by Heat Shock Proteins: Interest of Their Targeting in Cancer Therapy

Cobalt chloride affects the death of SH-SY5Y cells induced by inhibition of ubiquitin proteasome system. Role of heat shock protein 70 and caspase 3

Honey bee queens are vulnerable to heat-induced loss of fertility

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