Heat Shock Proteins 27 and 70: Anti-Apoptotic Proteins with Tumorigenic Properties

Garrido, Carmen; Brunet, Mathilde; Didelot, Céline; Zermati, Yaël; Schmitt, Élise; Kroemer, Guido

doi:10.4161/cc.5.22.3448

Cited by 629 publications

(615 citation statements)

References 117 publications

(157 reference statements)

Supporting

Mentioning

590

Contrasting

Unclassified

Order By: Relevance

“…Hsps can block both the intrinsic and the extrinsic apoptotic pathways through the interaction with proteins involved in the apoptotic process [30,31,33]. For example, high levels of Hsp27, or Hsp70, or Hsp90 inhibit apoptosis by preventing Caspase activation in a variety of cellular models [34][35][36]. However, the molecular mechanism of this anti-apoptotic effect mediated by Hsps is still unclear and it is possible that, under certain circumstances, may be due by a variety of different modulators [34].…”

Section: Discussionmentioning

confidence: 99%

“…For example, high levels of Hsp27, or Hsp70, or Hsp90 inhibit apoptosis by preventing Caspase activation in a variety of cellular models [34][35][36]. However, the molecular mechanism of this anti-apoptotic effect mediated by Hsps is still unclear and it is possible that, under certain circumstances, may be due by a variety of different modulators [34]. It has been shown that Hsp70 can inhibit apoptosis by interacting with a member of the Fas death-inducing signaling upstream of Caspase-8 [37,38].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex ( CubipyOXA ) leads to cell death in NCI-H292 cancer cells

Bavisotto

Nikolić

Gammazza

et al. 2017

Journal of Inorganic Biochemistry

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex ( CubipyOXA ) leads to cell death in NCI-H292 cancer cells

Bavisotto

Nikolić

Gammazza

et al. 2017

Journal of Inorganic Biochemistry

View full text Add to dashboard Cite

“…In addition, HSP also has critical roles in post-translational level, which maintains proteins in their correct configurations to ensure their stability and protect carcinoma cells from their apoptosis. 63 Overexpressed HSP70 increases levels of unfolded and denatured proteins in stressful cellular conditions. Therefore, HSP70 is considered to be important to maintain the functions of several housekeeping genes.…”

Section: Mirna In Hormone Receptor-positive/her2-negative Breast Cancermentioning

confidence: 99%

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

et al. 2016

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are short non-coding RNAs that regulate the function of target genes at the post-transcriptional phase. miRNAs are considered to have roles in the development, progression and metastasis of cancer. Recent studies have indicated that particular miRNA signatures are correlated with tumor aggressiveness, response to drug therapy and patient outcome in breast cancer. On the other hand, in routine clinical practice, the treatment regimens for breast cancer are determined based on the intrinsic subtype of the primary tumor. Previous studies have shown that miRNA expression profiles of each intrinsic subtypes of breast cancer differ. In hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, miRNA expressions are found to be correlated with endocrine therapy resistance, progesterone receptor expression and heat shock protein activity. Some miRNAs are associated with resistance to HER2-targeted therapy and HER3 expression in HER2-positive breast cancer. In triple-negative breast cancer, miRNA expressions are found to be associated with BRCA mutations, immune system, epithelial-mesenchymal transition, cancer stem cell properties and androgen receptor expression. As it has been clarified that the expression levels and functions of miRNA differ among the various subtypes of breast cancer, and it is necessary to take account of the characteristics of each breast cancer subtype during research into the roles of miRNA in breast cancer. In addition, the discovery of the roles played by miRNAs in breast cancer might provide new opportunities for the development of novel strategies for diagnosing and treating breast cancer.

show abstract

“…Following cellular stress (including the stress of oncogenesis), the expression levels of Hsp70 are increased via transcription factors HSF-1 and HIF-1 activation. In many cancers, this differential expression pattern is lost, with increased basal expression of Hsp70 documented in multiple tumor types [6]. Hsc70 and Hsp70 are members of the actin class of ATPases and exhibit high structural homology, especially within their ATPase domain [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…However, these chaperones have been shown to contribute to cancer cell survival via multiple anti-apoptotic functions [6,9] and increased expression of Hsp70 has been implicated in resistance to cytotoxic chemotherapeutics [10,11]. Selective knockdown of Hsp70 by both RNAi and antisense results in cell arrest and death in a variety of cancer cell lines [12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells

Massey¹,

Williamson²,

Browne³

et al. 2009

Cancer Chemother Pharmacol

273

254

View full text Add to dashboard Cite

Purpose The anti-apoptotic function of the 70 kDa family of heat shock proteins and their role in cancer is well documented. Dual targeting of Hsc70 and Hsp70 with siRNA induces proteasome-dependent degradation of Hsp90 client proteins and extensive tumor specific apoptosis as well as the potentiation of tumor cell apoptosis following pharmacological Hsp90 inhibition. Methods We have previously described the discovery and synthesis of novel adenosine-derived inhibitors of the 70 kDa family of heat shock proteins; the first inhibitors described to target the ATPase binding domain. The in vitro activity of VER-155008 was evaluated in HCT116, HT29, BT474 and MDA-MB-468 carcinoma cell lines. Cell proliferation, cell apoptosis and caspase 3/7 activity was determined for VER-155008 in the absence or presence of small molecule Hsp90 inhibitors. Results VER-155008 inhibited the proliferation of human breast and colon cancer cell lines with GI 50 s in the range 5.3-14.4 lM, and induced Hsp90 client protein degradation in both HCT116 and BT474 cells. As a single agent, VER-155008 induced caspase-3/7 dependent apoptosis in BT474 cells and non-caspase dependent cell death in HCT116 cells. VER-155008 potentiated the apoptotic potential of a small molecule Hsp90 inhibitor in HCT116 but not HT29 or MDA-MB-468 cells. In vivo, VER-155008 demonstrated rapid metabolism and clearance, along with tumor levels below the predicted pharmacologically active level. Conclusion These data suggest that small molecule inhibitors of Hsc70/Hsp70 phenotypically mimic the cellular mode of action of a small molecule Hsp90 inhibitor and can potentiate the apoptotic potential of a small molecule Hsp90 inhibitor in certain cell lines. The factors determining whether or not cells apoptose in response to Hsp90 inhibition or the combination of Hsp90 plus Hsc70/ Hsp70 inhibition remain to be determined.

show abstract

Heat Shock Proteins 27 and 70: Anti-Apoptotic Proteins with Tumorigenic Properties

Cited by 629 publications

References 117 publications

The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex ( CubipyOXA ) leads to cell death in NCI-H292 cancer cells

The dissociation of the Hsp60/pro-Caspase-3 complex by bis(pyridyl)oxadiazole copper complex ( CubipyOXA ) leads to cell death in NCI-H292 cancer cells

Recent trends in microRNA research into breast cancer with particular focus on the associations between microRNAs and intrinsic subtypes

A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells

Contact Info

Product

Resources

About