SIRT2 Expression Is Higher in Uveal Melanoma than In Ocular Melanocytes

Halfed, Danielle G.; Zoroquiaín, Pablo; Wood, Henry A; Blanco, Paula; AlSaati, Nouf; Aldrees, Sultan; Bravo-Filho, Vasco; Burnier, Miguel N

doi:10.1159/000439309

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…A recent study (n = 21) demonstrated significantly higher SIRT2 immunostaining in uveal melanoma cells compared to normal melanocytes, suggesting a role as an oncogene and therapeutic target [33]. However, in our study (n = 14), we noticed a range of staining of uveal melanoma cells for HDAC6 and SIRT2.…”

Section: Discussioncontrasting

confidence: 87%

Tumour Expression of Histone Deacetylases in Uveal Melanoma

et al. 2018

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Purpose: To determine the expression of histone deacetylase enzymes in uveal melanoma tumour cells. Procedures: This is an observational immunohistochemical study of 16 formalin-fixed, paraffin-embedded eyes enucleated for uveal melanoma between January 2001 and March 2002. Haematoxylin and eosin paraffin sections were reviewed for histopathological parameters according to the American Joint Committee on Cancer 7th edition. Sections were then immunohistochemically stained for histone deacetylases 1, 2, 3, 4 and 6 and sirtuin 2 using an automated Leica Bond II platform and Fast Red chromogen, then digitally scanned using Aperio software before assessment of staining. Results: Nuclear expression of histone deacetylases 1, 2, 3, 4 and 6 and of sirtuin 2 was confirmed in uveal melanoma tumour cells. In addition, the tumour cells showed cytoplasmic expression of histone deacetylases 4 and 6 and sirtuin 2. Nuclear and cytoplasmic immunostaining was also seen in intraocular tissues uninvolved by the tumour. Conclusion: Uveal melanoma tumour cells express histone deacetylases 1, 2, 3, 4 and 6 and sirtuin 2, confirming potential tissue targets for histone deacetylase inhibitors.

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Section: Discussioncontrasting

confidence: 87%

Tumour Expression of Histone Deacetylases in Uveal Melanoma

et al. 2018

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“…However, increasing evidence suggests that SIRT2 may also be a pro-oncogenic factor. SIRT2 expression is up-regulated in hepatocellular carcinoma ( 11 ), renal cell carcinoma ( 16 ), prostate cancer ( 17 , 18 ), basal-like breast cancer ( 19 ), uveal melanoma ( 20 ), and acute myeloid leukemia ( 21 ). SIRT2 not only increases the proliferation and metastasis ability of bladder and gastric cancer cells ( 22 , 23 ) but also promotes the occurrence and development of hepatocellular and breast carcinomas ( 11 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis

Yi¹,

Zhang

Wang³

et al. 2021

Sci. Adv.

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Improper distribution of chromosomes during mitosis can contribute to malignant transformation. Higher eukaryotes have evolved a mitotic catastrophe mechanism for eliminating mitosis-incompetent cells; however, the signaling cascade and its epigenetic regulation are poorly understood. Our analyses of human cancerous tissue revealed that the NAD-dependent deacetylase SIRT2 is up-regulated in early-stage carcinomas of various organs. Mass spectrometry analysis revealed that SIRT2 interacts with and deacetylates the structural maintenance of chromosomes protein 1 (SMC1A), which then promotes SMC1A phosphorylation to properly drive mitosis. We have further demonstrated that inhibition of SIRT2 activity or continuously increasing SMC1A-K579 acetylation causes abnormal chromosome segregation, which, in turn, induces mitotic catastrophe in cancer cells and enhances their vulnerability to chemotherapeutic agents. These findings suggest that regulation of the SIRT2-SMC1A axis through deacetylation-phosphorylation permits escape from mitotic catastrophe, thus allowing early precursor lesions to overcome oncogenic stress.

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“…15 In addition, a recent study has shown that SIRT2 levels were higher in uveal melanoma compared to normal melanocytes. 16 Based on the known functions of SIRT1 in cancer, it is presumed that a specific inhibitor of SIRT1 would be the preferable treatment, but since the status and role of SIRT2 in cutaneous melanoma are currently unknown, further investigation is required. Therefore, as an adjunct to our published studies regarding the use of SIRT1/ SIRT2 combination therapies in melanoma, here, we evaluate the endogenous expression of SIRT2 protein in a small array of melanoma tissue samples.…”

Section: Introductionmentioning

confidence: 99%

Expression profile of SIRT2 in human melanoma and implications for sirtuin-based chemotherapy

et al. 2017

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Melanoma is cancer of melanin-containing melanocyte cells. This neoplasm is one of the most deadly forms of skin cancer, and currently available therapeutic options are insufficient in significantly improve outcomes for many patients. Therefore, novel targets are required to effectively manage this neoplasm. Several sirtuins have previously been found to be upregulated in melanoma, so in this study, the expression profile of SIRT2 was determined. Employing a tissue microarray containing benign nevi, primary melanomas, and lymph node metastases, we have found that the tissue from lymph node metastases appears to have a significant upregulation of SIRT2 relative to primary tumors across the nuclear, cytoplasmic, and whole cell data. Additionally, SIRT2 staining was found to be higher in the nucleus of metastatic melanomas compared to cytoplasmic staining. As SIRT2 is considered to be a predominantly cytoplasmic protein, this is a novel and very interesting finding. This, combined with previous studies that show other sirtuins are increased in melanoma and involved in cellular proliferation and survival, leads to the suggestion that exploring pan-sirtuin inhibitors may be the best target for the next iteration of melanoma chemotherapeutics.

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SIRT2 Expression Is Higher in Uveal Melanoma than In Ocular Melanocytes

Cited by 5 publications

References 23 publications

Tumour Expression of Histone Deacetylases in Uveal Melanoma

Tumour Expression of Histone Deacetylases in Uveal Melanoma

The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis

Expression profile of SIRT2 in human melanoma and implications for sirtuin-based chemotherapy

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