The Levels of H11/HspB8 DNA Methylation in Human Melanoma Tissues and Xenografts Are a Critical Molecular Marker for 5-Aza-2′-Deoxycytidine Therapy

Smith, Cynthia C.; Li, Baiquan; Liu, Juan; Lee, Kie-Sok; Aurelian, Laure

doi:10.3109/07357907.2011.584588

Cited by 19 publications

(32 citation statements)

References 56 publications

(100 reference statements)

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“…It's expression is reduced in melanoma, prostate cancer, Ewing's sarcoma and hematologic malignancies through aberrant DNA methylation. The levels of inhibition strongly correlate with those of DNA methylation (p < .001), suggesting that HspB8 may serve as a marker for de-methylating therapeutics (Smith et al, 2011). In these tumors, restored HspB8 expression induces cell death and inhibits tumor growth in xenograft models (Gober et al, 2003;Gober et al, 2005;Cui et al, 2012).…”

Section: Inhibition Of Unfolded Protein Response (Upr)mentioning

confidence: 95%

“…However, its expression is not always heat inducible and it can be upregulated by diverse stress conditions. For example, HspB8 expression is not heat-inducible in melanocytes (Smith et al, 2011) and it is upregulated by sublethal sodium arsenite and oxidative and hyperosmotic stress in neurons, where it likely contributes protective activity (Bartelt- Kirbach and Golenhofen, 2014). DNA methylation and the regulation of expression/function HspB8 differs from other Hsps in that its expression in human cells is subject to methylation-associated repression.…”

Section: Stress-induced Expressionmentioning

confidence: 99%

“…Tumor suppressor HspB8 has tumor suppressor activity. It is expressed in human melanocytes, where it functions as a cell cycle regulator and causes growth arrest through β-catenin phosphorylation at the transcriptional activity site Ser(552) and inhibition of the cell-cycle regulatory proteins cyclin E/Cdk2 that control G1 to S transition (Smith et al, 2011). In melanoma and other cancers, its expression is inhibited through aberrant DNA methylation and restored expression through treatment with demethylating agents causes cell death and inhibits tumor growth Smith et al, 2012;Cui et al, 2012).…”

Section: Inhibition Of Unfolded Protein Response (Upr)mentioning

confidence: 99%

“…Also characteristic of tumor suppressors, such as p53, is the cell-type specificity of the HspB8 effects and the finding that it can undergo single-site mutation to lose its activity or to acquire neoplastic potential. This is respectively exemplified by the natural mutants P173H, which is inactive, and W51C, which has proliferative (anti-apoptotic) activity (Gober et al, 2003;Smith et al, 2011;Smith et al, 2012). However, the frequency of such naturally occurring mutations is still unknown.…”

Section: Inhibition Of Unfolded Protein Response (Upr)mentioning

confidence: 99%

“…The role of HspB8 as a tumor suppressor is further supported by the finding of a pro-tumorigenic mutation associated with increased autokinase activity (W51C). This mutation indicates that the autokinase activity is required for the HspB8 proliferative, but not anti-proliferative (pro-apoptotic) activity (Gober et al, 2003;Smith et al, 2011;Smith et al, 2012).…”

Section: Melanoma and Other Cancersmentioning

confidence: 99%

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HSPB8 (heat shock 22kDa protein 8)

Bollino¹,

Aurelian²

2014

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Section: Inhibition Of Unfolded Protein Response (Upr)mentioning

confidence: 95%

Section: Stress-induced Expressionmentioning

confidence: 99%

Section: Inhibition Of Unfolded Protein Response (Upr)mentioning

confidence: 99%

Section: Inhibition Of Unfolded Protein Response (Upr)mentioning

confidence: 99%

Section: Melanoma and Other Cancersmentioning

confidence: 99%

See 3 more Smart Citations

HSPB8 (heat shock 22kDa protein 8)

Bollino¹,

Aurelian²

2014

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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Promoter methylation as biomarkers for diagnosis of melanoma: A systematic review and meta‐analysis

Guo

Long

Lei

2018

Journal Cellular Physiology

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Melanoma is one of the most common skin cancer that is characterized by rapid growth, early metastasis, high malignant, and mortality. Accumulating evidence demonstrated that promoter methylation of tumor-suppressor genes is implicated in the pathogenesis of melanoma. In the current study, we performed a meta-analysis to identify promising methylation biomarkers in the diagnosis of melanoma. We carried out a systematic literature search using Pubmed, Embase, and ISI web knowledge database and found that gene promoter methylation of 50 genes was reported to be associated with the risk of melanoma. Meta-analysis revealed that hypermethylation of claudin 11 (CLDN11; odds ratio [OR], 16.82; 95% confidence interval [CI], 1.97-143.29; p = 0.010), O-6-methylguanine-DNA methyltransferase (MGMT; OR, 5.59; 95% CI, 2.51-12.47; p < 0.0001), cyclindependent kinase inhibitor 2A (p16; OR, 6.57; 95% CI, 2.19-19.75; p = 0.0008), retinoic acid receptor β (RAR-β2; OR, 24.31; 95% CI, 4.58-129.01; p = 0.0002), and Ras association domain family member (RASSF1A; OR, 9.35; 95% CI, 4.73-18.45; p < 0.00001) was significantly higher in melanoma patients compared with controls. CLDN11 (OR, 14.52; 95% CI, 1.84-114.55; p = 0.01), MGMT (OR, 8.08; 95% CI,; p = 0.006), p16 (OR, 9.44; 95% CI,; p = 0.0005), and RASSF1A (OR, 7.72; 95% CI, 1.05-56.50; p = 0.04) hypermethylation was significantly increased in primary melanoma compared with controls. Methylation frequency of CLDN11 (OR, 25.56; 95% CI, 2.32-281.66; p = 0.008), MGMT (OR, 4.64; 95% CI, 1.98-10.90; p = 0.0004), p16 (OR, 4.31; 95% CI,; p = 0.01), and RASSF1A (OR, 10.10; 95% CI, 2.87-35.54; p = 0.0003) was significantly higher in metastasis melanoma compared with controls. These findings indicated that CLDN11, MGMT, p16, RAR-β2, and RASSF1A hypermethylation is a risk factor and a potential biomarker for melanoma. CLDN11, MGMT, p16, and RASSF1A promoter methylation may take part in the development of melanoma and become useful biomarkers in the early diagnosis of the disease.

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Immense Cellular Implications Associated to Small Stress Proteins Expression: Impacts on Human Pathologies

Arrigo

Ducarouge

Lavial

et al. 2015

Heat Shock Proteins

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In addition to being potent chaperones that protect cells against the accumulation of unfolded proteins under stress conditions, mammalian small heat shock proteins (small Hsps) regulate many vital cellular processes in normal and pathological cells. Indeed, these Hsps are constitutively expressed in many tissues and show dramatic changes in their levels of expression in most human pathologies. They are characterized by a large spectrum of activities and are particularly active in protein conformational and infl ammatory diseases as well as in cancer pathologies. It is now believed that the immense cellular implications of small Hsps results from their ability to interact, through particular structural changes, with many different client proteins that are subsequently modulated in their activities or half-lifes. Here, we have integrated functionally and structurally the recent data in the literature concerning the interactions of mammalian small Hsps with specifi c clients. Further analysis with geneMANIA software and database confi rmed the incredibly large number of functions associated with these Hsps. The consequences for human pathologies as well as putative therapeutic strategies are discussed, particularly when the expression of small Hsps is harmful (as in some cancer pathologies) or when it appears benefi cial for patients.

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The Levels of H11/HspB8 DNA Methylation in Human Melanoma Tissues and Xenografts Are a Critical Molecular Marker for 5-Aza-2′-Deoxycytidine Therapy

Cited by 19 publications

References 56 publications

HSPB8 (heat shock 22kDa protein 8)

HSPB8 (heat shock 22kDa protein 8)

Promoter methylation as biomarkers for diagnosis of melanoma: A systematic review and meta‐analysis

Immense Cellular Implications Associated to Small Stress Proteins Expression: Impacts on Human Pathologies

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