scholarly journals Heat shock proteins and cancer: intracellular chaperones or extracellular signalling ligands?

2017 ◽  
Vol 373 (1738) ◽  
pp. 20160524 ◽  
Author(s):  
Stuart K. Calderwood
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Tumour Cells ◽  
Future Studies ◽  
Proteotoxic Stress ◽  
Wide Range ◽  
Window Of Vulnerability ◽  
Shock Proteins ◽  
Extracellular Signalling ◽  
Key Questions

Heat shock proteins (HSPs) are found at elevated concentrations in tumour cells, and this increase reflects the proteotoxic stress experienced by the cells due to expanding levels of the mutated oncoproteins that drive tumorigenesis. The protection of oncogenic proteins by HSPs offers a window of vulnerability in tumour metabolism that has been exploited using Hsp90-targeting drugs. Such compounds have been shown to cause inhibition and degradation of a wide range of proteins essential for oncogenesis. Recently, Hsp90 has also been shown to be secreted by tumour cells and to interact in autocrine or paracrine manners with the surfaces of adjacent cells, leading to increased growth and metastasis. Future studies will address a number of key questions associated with these findings, including the relative importance of intracellular versus extracellular HSPs in tumorigenesis, as well as overcoming potential problems with normal tissue toxicity associated with Hsp90 drugs. Targeting individual members of HSP families and inactivating extracellular HSPs may be desirable future approaches that offer increased selectivity in targeting HSPs in cancer. This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.

Expression of heat shock proteins in medulloblastoma

2013 ◽  
Vol 12 (5) ◽  
pp. 452-457 ◽  
Author(s):  
George A. Alexiou ◽  
George Vartholomatos ◽  
Kalliopi Stefanaki ◽  
Amalia Patereli ◽  
Lefkothea Dova ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Significant Positive Correlation ◽  
Large Cell ◽  
Hsp70 Expression ◽  
Ki 67 ◽  
Positive Correlation ◽  
Wide Range ◽  
Shock Proteins ◽  
Multiplex Bead

Object Medulloblastoma (MB) is the most common malignant brain tumor in children. Heat shock proteins (HSPs) comprise a superfamily of proteins that serve as molecular chaperones and are overexpressed in a wide range of human cancers. The purpose of the present study was to investigate the expression of HSP27 (pSer82), HSP27 (pSer15), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt by multiplex bead array assay of MBs. The results of HSP and Akt expression were correlated with MB subtype; immunohistochemical expression of Ki-67 index, bcl-2, and p53; and patients' prognosis. Methods The authors retrospectively evaluated 25 children with MB who underwent surgery. Immunohistochemical analysis of Ki-67, p53, and bcl-2 expression was performed in all cases. By using multiplex bead array assay, a simultaneous detection of HSP27 (pSer82), HSP27 (pSer15), HSP40, HSP60, HSP70, HSP90-α, Akt, and phospho-Akt was performed. Results Medulloblastoma with extensive nodularity had significantly lower HSP27 (pSer15) expression (p = 0.039) but significantly higher HSP60 expression (p = 0.021) than classic MB. Large-cell MB had significantly higher HSP70 expression (p = 0.028) than classic MB. No significant difference was found between HSP27 (pSer82), HSP40, HSP90-α, Akt, or phospho-Akt expression and MB subtype. Large-cell MBs had significantly higher Ki-67 index compared with classic MBs (p = 0.033). When analyzing all MBs, there was a significant negative correlation between HSP27 (pSer15) and Ki-67 index (r = −0.475, p = 0.016); a significant positive correlation between HSP70 expression and Ki-67 index (r = 0.407, p = 0.043); and a significant positive correlation between HSP70 expression and bcl-2 index (r = 0.491, p = 0.023). Patients with large-cell MB had a worse survival than those with classic MB, but the difference did not reach statistical significance (p = 0.076). Conclusions A substantial expression of several HSPs in MB was observed. Given that HSPs represent an attractive strategy for anticancer therapy, further studies, involving larger series of patients, are obviously necessary to clarify the relationship of HSPs with tumor aggressiveness and prognosis.

scholarly journals Heat shock proteins – modulators of apoptosis in tumour cells

Leukemia ◽  
2000 ◽  
Vol 14 (7) ◽  
pp. 1161-1173 ◽  
Author(s):  
EM Creagh ◽  
D Sheehan ◽  
TG Cotter
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Tumour Cells ◽  
Shock Proteins

scholarly journals Prognostic and Functional Significant of Heat Shock Proteins (HSPs) in Breast Cancer Unveiled by Multi-Omics Approaches

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 247
Author(s):  
Miriam Buttacavoli ◽  
Gianluca Di Cara ◽  
Cesare D’Amico ◽  
Fabiana Geraci ◽  
Ida Pucci-Minafra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cancer Progression ◽  
Prognostic Significance ◽  
Molecular Size ◽  
Good Prognosis ◽  
Mesenchymal Transition ◽  
Wide Range ◽  
Shock Proteins

Heat shock proteins (HSPs) are a well-characterized molecular chaperones protein family, classified into six major families, according to their molecular size. A wide range of tumors have been shown to express atypical levels of one or more HSPs, suggesting that they could be used as biomarkers. However, the collective role and the possible coordination of HSP members, as well as the prognostic significance and the functional implications of their deregulated expression in breast cancer (BC) are poorly investigated. Here, we used a systematic multi-omics approach to assess the HSPs expression, the prognostic value, and the underlying mechanisms of tumorigenesis in BC. By using data mining, we showed that several HSPs were deregulated in BC and significantly correlated with a poor or good prognosis. Functional network analysis of HSPs co-expressed genes and miRNAs highlighted their regulatory effects on several biological pathways involved in cancer progression. In particular, these pathways concerned cell cycle and DNA replication for the HSPs co-expressed genes, and miRNAs up-regulated in poor prognosis and Epithelial to Mesenchymal Transition (ETM), as well as receptors-mediated signaling for the HSPs co-expressed genes up-regulated in good prognosis. Furthermore, the proteomic expression of HSPs in a large sample-set of breast cancer tissues revealed much more complexity in their roles in BC and showed that their expression is quite variable among patients and confined into different cellular compartments. In conclusion, integrative analysis of multi-omics data revealed the distinct impact of several HSPs members in BC progression and indicate that collectively they could be useful as biomarkers and therapeutic targets for BC management.

scholarly journals Short Review on Types of Heat Shock Proteins and Their Fundamental Characters for Body Maintenance Together With Role in Cancer

2020 ◽  
pp. 103-108
Author(s):  
Muhammad Muneeb ◽  
Moazam Ali ◽  
Tahir Sarfaraz ◽  
Wajid Ali ◽  
Zeeshan Ahmad Bhutta
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Heat Shock Protein ◽  
Significant Role ◽  
Cancer Diagnosis ◽  
Short Review ◽  
The Body ◽  
Normal Functions ◽  
Wide Range ◽  
Shock Proteins

Body of living thing is a complex machine that works on multifunctional processes and needs maintenance. Heat shock protein is a specific type of protein that cares about many normal functions of the body. These proteins have many dynamic occupations to shield the body from various diseases and also a key role in the coiling and uncoiling of proteins, prevent from apoptosis and transportation of proteins. Along with these all properties, the foremost function of these proteins is prevention from cancer and a significant role in cancer diagnosis. Commonly heat shock protein known as chaperones and a wide range of their types have been discovered with their functions as well. Recently many scientists are working on additional investigation of heat shock proteins. This review concludes some basic types of heat shock proteins and their elegant purposes and also providing an open eye for new scientist about a further investigation of heat shock protein.

scholarly journals Direct Sunlight Influences Postharvest Temperature Responses and Ripening of Five Avocado Cultivars

2000 ◽  
Vol 125 (3) ◽  
pp. 370-376 ◽  
Author(s):  
Allan B. Woolf ◽  
Asya Wexler ◽  
Dov Prusky ◽  
Elana Kobiler ◽  
Susan Lurie
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Chilling Injury ◽  
Persea Americana ◽  
Hot Water ◽  
Class I ◽  
The Sun ◽  
Direct Sunlight ◽  
Wide Range ◽  
Shock Proteins

Effect of direct sunlight on the postharvest behavior of five avocado (Persea americana Mill.) cultivars (Ettinger, Fuerte, Hass, Horshim and Pinkerton) was examined. Probes placed 6 to 7 mm under the peel showed that the temperature an the side exposed to the sun could be as much as 15 to 20 °C higher than the temperature of shade fruit, while the nonexposed side of the fruit was ≈5 °C higher than the shade fruit. With the exception of `Ettinger', sun fruit, and especially the exposed side, were found to be most tolerant to postharvest 50 and 55 °C hot water treatments. Similarly, storage of fruit at 0 °C for between 3 to 6 weeks caused severe chilling injury to shade fruit, with less effect on sun fruit. Furthermore, there was little or no damage on the exposed side of the sun fruit. During postharvest ripening at 20 °C, sun fruit showed a delay of between 2 to 5 days in their ethylene peak compared with shade fruit. The exposed side of the sun fruit was generally firmer than the nonexposed side, and the average firmness was higher than that of shade fruit. Activities of polygalacturonase and cellulase were similar in shade and sun fruit of similar firmness. After inoculation with Colletotrichum gloeosporioides (Penz.) Penz@sacc., the appearance of lesions on sun fruit occurred 2 to 3 days after shade fruit. Levels of heat-shock proteins were examined using western blotting with antibodies for Class I and II cytoplasmic heat-shock proteins. Class I reacted with proteins from the exposed side of sun fruit and Class II with proteins from both sides of sun fruit. Thus, it is clear that preharvest exposure of fruit to the sun can result in a wide range of postharvest responses.

Evidence for protein damage at environmental temperatures: seasonal changes in levels of ubiquitin conjugates and hsp70 in the intertidal mussel Mytilus trossulus

1995 ◽  
Vol 198 (7) ◽  
pp. 1509-1518 ◽  
Author(s):  
G Hofmann ◽  
G Somero
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Protein Damage ◽  
Mytilus Trossulus ◽  
Energy Demands ◽  
Wide Range ◽  
Intertidal Mussel ◽  
Shock Proteins ◽  
Ubiquitin Conjugate ◽  
Mussel Mytilus Trossulus

We examined the seasonal variation in environmentally induced protein damage in natural populations of the intertidal mussel Mytilus trossulus. In order to compare the state of protein pools during seasonal variations in environmental temperature, we used solid-phase immunochemical analysis to quantify ubiquitin conjugate concentrations and relative levels of the stress protein hsp70. The two biochemical indices were selected for their cellular roles in irreversible and reversible protein denaturation, respectively. Proteins that are ubiquitinated are irreversibly damaged and are degraded by intracellular proteases; stress proteins act as molecular chaperones to re-fold thermally denatured proteins and, thus, indicate degrees of reversible protein damage. Comparisons involved mussels collected in February and August from two study sites: an intertidal site which subjected animals to a wide range of body temperatures (from approximately 10 to 35 C in summer), and a subtidal site where animals remained submerged throughout the tidal cycle. Our results show that quantities of ubiquitin conjugates and hsp70 were greater in gill tissue from summer-collected mussels than in gills of winter-collected specimens. Ubiquitin conjugate and hsp70 levels were also greater in mussels collected from an intertidal location than in mussels from a submerged population. Our results show that the high summer temperatures normally experienced in the field are sufficient to cause increased denaturation of cellular proteins. Despite increases in the concentrations of heat shock proteins in summer-acclimatized mussels, elevated levels of irreversibly denatured, i.e. ubiquitinated, proteins were still observed, which indicates that the heat shock response may not be able to rescue all heat-damaged proteins. The energy costs associated with replacing heat-damaged proteins and with maintaining the concentrations and activities of heat shock proteins may contribute substantially to cellular energy demands. These increased energy demands may have an impact on the ecological energetic relationships of species, e.g. in the allocations of energy for growth and reproduction, and, as a consequence, may contribute to determining their distribution limits.

The Role of Heat Shock Proteins in Cisplatin Resistance

2019 ◽  
Vol 18 (15) ◽  
pp. 2093-2109 ◽  
Author(s):  
Zdzisław Krawczyk ◽  
Agnieszka Gogler-Pigłowska ◽  
Damian R. Sojka ◽  
Dorota Scieglinska
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cancer Cells ◽  
Relevant Information ◽  
Multiple Observations ◽  
Wide Range ◽  
Cellular Context ◽  
Universal Relationship ◽  
Shock Proteins

Background: Cisplatin (CDDP), a small molecule platinum-based compound, is an effective anticancer drug used against a wide range of human neoplasms. Long-term clinical use of CDDP is however limited due to the development of drug resistance and the possible incidence of serious side effects including nephrotoxicity and ototoxicity. The mechanisms underlying resistance of cells to CDDP are complex, and among them, the cytoprotective involvement of proteins referred to as Heat Shock Proteins (HSP) seems potentially important. Methods: We searched various electronic databases including PubMed and selected the reports concerning the contribution of HSPs to CDDP resistance of cancer cells and to minimize the CDDP-induced nephrotoxicity and ototoxicity. Results: This critical review of data collected so far summarizes the results on the major HSPs: HSP27/HSPB1, HSP70/HSPA1, HSP90/HSPC and GRP78/HSPA5, because only these have been the subject of the most intense research in the matter discussed here. We also provide relevant information concerning some other HSPs, namely HSPA9/mortalin, HSPA2, HSP110 and DNAJ. A possible role of HSPs in counteracting CDDP-induced neprho- and ototoxicity is mentioned. Conclusions: This review shows that no universal relationship between the levels of expression of HSPs and sensitivity of cancer cells to CDDP can be confirmed. Multiple observations indicate however that such correlation can rather manifest as a molecular or cellular context-dependent phenomenon. Thus, HSPs can be viewed as an important component of the multifactorial, complex response of cancer cells to CDDP. However, to strengthen such a conviction, more extensive studies are needed.

scholarly journals Influence Of Total Body Controlled Hyperthermic Perfusion on Levels of Heat Shock Proteins 70 kDa in Patients with Active Infective Endocarditis

2019 ◽  
pp. 14-26
Author(s):  
A. A. Krikunov ◽  
A. B. Koltunova
Keyword(s):  
Infective Endocarditis ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
General Tendency ◽  
Hsp 70 ◽  
Total Blood ◽  
Wide Range ◽  
Total Body ◽  
Shock Proteins ◽  
The Relationship

Development of infective endocarditis initiates a complex immunological response of the organism changing over time: the prevalence of pro-and anti-inflammatory mechanisms at the beginning is replaced by immunosuppression. A significant role in antigen presentation, cross-presentation, activation of macrophages and lymphocytes play the heat shock proteins 70 kDa (HSP). The aim of the study was to investigate the relationship between systemic inflammatory response and HSP 70 kDa values in patients operated on under the total body controlled hyper-thermic perfusion (TBCHP). Materials and methods.The study included 18 patients with active infective valve endocarditis operated from 01.01.2016 to 01.01.2017 with the use of TBCHP. Assessment of the relationship between clinical characteristics of patients with infective endocarditis and the level of heat shock protein 70 kDa was performed preoperatively, 2 hours after TBCHP, 8 hours after TBCHP, 20 hours after TBCHP. Results.The presence of high levels of heat shock proteins 70 kDa (5.6 ± 3.3 ng/ml) pre-operatively indicated the depression of cellular and humoral immunity. Reduction in total blood plasma protein level as an indicator of catabolism was also combined with the registration of higher values of HSP70 kDa. After 2 hours after TBCHP a wide range of HSP 70 kDa levels was observed. A blood test performed after 2 hours after TBCHP showed HSP70 kDa – average level of 6.06 ± 3.8 ng/ml. Values range between 0.96 to 9.08 ng/ml. According to these data it was possible to distinguish two subgroups of patients who differ significantly in the average values of HSP70 kDa after TBCHP. There was a general tendency to reduce the values of HSP 70kDa from the initial preoperative level to the end of 20 hour after TBCHP – 5.6 ± 3.3 ng/ml and 1.6 ± 0.68 ng/ml correspondingly (p = 0.116). Conclusion. Taking into account the previously identified preoperative relationships between HSP70 kDa level and clinical parameters of patients we may suggest that reduction of HSP 70 kDa corresponds with elimination of signs of the syndrome of persistent inflammation, immunosuppression and catabolism.

scholarly journals The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis

2017 ◽  
Vol 373 (1738) ◽  
pp. 20160525 ◽  
Author(s):  
Chengkai Dai
Keyword(s):  
Stress Response ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Protein Misfolding ◽  
Heat Shock Factor 1 ◽  
Growth And Survival ◽  
Proteotoxic Stress ◽  
Shock Proteins ◽  
Misfolding Diseases

The heat-shock, or HSF1-mediated proteotoxic stress, response (HSR/HPSR) is characterized by induction of heat-shock proteins (HSPs). As molecular chaperones, HSPs facilitate the folding, assembly, transportation and degradation of other proteins. In mammals, heat shock factor 1 (HSF1) is the master regulator of this ancient transcriptional programme. Upon proteotoxic insults, the HSR/HPSR is essential to proteome homeostasis, or proteostasis, thereby resisting stress and antagonizing protein misfolding diseases and ageing. Contrasting with these benefits, an unexpected pro-oncogenic role of the HSR/HPSR is unfolding. Whereas HSF1 remains latent in primary cells without stress, it becomes constitutively activated within malignant cells, rendering them addicted to HSF1 for their growth and survival. Highlighting the HSR/HPSR as an integral component of the oncogenic network, several key pathways governing HSF1 activation by environmental stressors are causally implicated in malignancy. Importantly, HSF1 impacts the cancer proteome systemically. By suppressing tumour-suppressive amyloidogenesis, HSF1 preserves cancer proteostasis to support the malignant state, both providing insight into how HSF1 enables tumorigenesis and suggesting disruption of cancer proteostasis as a therapeutic strategy. This review provides an overview of the role of HSF1 in oncogenesis, mechanisms underlying its constitutive activation within cancer cells and its pro-oncogenic action, as well as potential HSF1-targeting strategies. This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.

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