Membrane-Associated Heat Shock Proteins in Oncology: From Basic Research to New Theranostic Targets

Shevtsov, Maxim; Balogi, Zsolt; Khachatryan, W. А.; Gao, Huile; Vı́gh, László; Multhoff, Gabriele

doi:10.3390/cells9051263

Cited by 54 publications

(45 citation statements)

References 180 publications

(247 reference statements)

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“…Whereas, HSP60 (HSPD1) is found in mitochondria [ 74 ]. Some HSPs can also be found on the cell surface, such as HSP60 and HSP70, especially in lipid rafts (plasma membrane subdomains, containing high levels of cholesterol and glycosphingolipids) [ 75 ]. More recently, HSPs are considered key players in the intercellular cross-talk [ 76 ].…”

Section: Discussionmentioning

confidence: 99%

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

Buttacavoli

Cara

D’Amico

et al. 2021

Biology

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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.

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Section: Discussionmentioning

confidence: 99%

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

Buttacavoli

Cara

D’Amico

et al. 2021

Biology

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“…Thus, HSF and HSP can be an important target for MDR reversibility [ 49 , 50 ]. Numerous studies have shown the relationship between membrane-associated HSP and drug resistance and the possibility to use HSP as biomarkers for tumor detection [ 51 ]. The results of our study showed that the basal level of expression of the hsc70 and grp78 genes was significantly higher in RJKEB cells with MDR phenotype.…”

Section: Discussionmentioning

confidence: 99%

Impact of Polyallylamine Hydrochloride on Gene Expression and Karyotypic Stability of Multidrug Resistant Transformed Cells

Алексеенко

Шилина

Kozhukharova

et al. 2020

Cells

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The synthetic polymer, polyallylamine hydrochloride (PAA), is found in a variety of applications in biotechnology and medicine. It is used in gene and siRNA transfer, to form microcapsules for targeted drug delivery to damaged and tumor cells. Conventional chemotherapy often does not kill all cancer cells and leads to multidrug resistance (MDR). Until recently, studies of the effects of PAA on cells have mainly focused on their morphological and genetic characteristics immediately or several hours after exposure to the polymer. The properties of the cell progeny which survived the sublethal effects of PAA and resumed their proliferation, were not monitored. The present study demonstrated that treatment of immortalized Chinese hamster cells CHLV-79 RJK sensitive (RJK) and resistant (RJKEB) to ethidium bromide (EB) with cytotoxic doses of PAA, selected cells with increased karyotypic instability, were accompanied by changes in the expression of p53 genes c-fos, topo2-α, hsp90, hsc70. These changes did not contribute to the progression of MDR, accompanied by the increased sensitivity of these cells to the toxic effects of doxorubicin (DOX). Our results showed that PAA does not increase the oncogenic potential of immortalized cells and confirmed that it can be used for intracellular drug delivery for anticancer therapy.

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“…Hsps perform important functions in maintaining protein homeostasis, such as mediating protein folding, assembly, and intracellular localization and regulating apoptosis. Failure of these processes may lead to disease ( 1 ).…”

Section: Introductionmentioning

confidence: 99%

The Mitochondrial Chaperone TRAP1 as a Candidate Target of Oncotherapy

et al. 2021

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Tumor necrosis factor receptor-associated protein 1 (TRAP1), a member of the heat shock protein 90 (Hsp90) chaperone family, protects cells against oxidative stress and maintains mitochondrial integrity. To date, numerous studies have focused on understanding the relationship between aberrant TRAP1 expression and tumorigenesis. Mitochondrial TRAP1 is a key regulatory factor involved in metabolic reprogramming in tumor cells that favors the metabolic switch of tumor cells toward the Warburg phenotype. In addition, TRAP1 is involved in dual regulation of the mitochondrial apoptotic pathway and exerts an antiapoptotic effect on tumor cells. Furthermore, TRAP1 is involved in many cellular pathways by disrupting the cell cycle, increasing cell motility, and promoting tumor cell invasion and metastasis. Thus, TRAP1 is a very important therapeutic target, and treatment with TRAP1 inhibitors combined with chemotherapeutic agents may become a new therapeutic strategy for cancer. This review discusses the molecular mechanisms by which TRAP1 regulates tumor progression, considers its role in apoptosis, and summarizes recent advances in the development of selective, targeted TRAP1 and Hsp90 inhibitors.

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Membrane-Associated Heat Shock Proteins in Oncology: From Basic Research to New Theranostic Targets

Cited by 54 publications

References 180 publications

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

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

Impact of Polyallylamine Hydrochloride on Gene Expression and Karyotypic Stability of Multidrug Resistant Transformed Cells

The Mitochondrial Chaperone TRAP1 as a Candidate Target of Oncotherapy

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