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Published on: February 27, 2016
Expression profile of SIRT2 in human melanoma and implications for sirtuin-based chemotherapy
Melissa Jean Wilking-Busch1, Mary Ann Ndiaye1, Wei Huang2
1a Department of Dermatology , University of Wisconsin , Madison , WI , USA.
Abstract:
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.
Insights
This study reveals that SIRT2 protein is significantly upregulated in metastatic melanoma, particularly in the nucleus. This finding suggests targeting sirtuins may offer new therapeutic strategies for melanoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Melanoma, a deadly skin cancer, has limited therapeutic options.
- Sirtuins (SIRTs) are implicated in cancer, with several found upregulated in melanoma.
- Novel therapeutic targets are crucial for improving melanoma patient outcomes.
Purpose of the Study:
- To investigate the expression profile of Sirtuin 2 (SIRT2) in melanoma.
- To determine if SIRT2 expression differs between primary melanomas and metastatic lesions.
- To explore the subcellular localization of SIRT2 in melanoma.
Main Methods:
- Utilized a tissue microarray containing benign nevi, primary melanomas, and lymph node metastases.
- Quantified SIRT2 expression levels across nuclear, cytoplasmic, and whole cell compartments.
- Compared SIRT2 staining intensity in different melanoma stages.
Main Results:
- SIRT2 expression was significantly upregulated in lymph node metastases compared to primary melanomas.
- SIRT2 staining was notably higher in the nucleus of metastatic melanomas.
- This nuclear localization is novel, as SIRT2 is typically considered a cytoplasmic protein.
Conclusions:
- Increased nuclear SIRT2 in metastatic melanoma represents a significant finding.
- Combined with other sirtuins' roles in proliferation and survival, this suggests targeting SIRT2 is a promising therapeutic avenue.
- Pan-sirtuin inhibitors may represent the next generation of melanoma chemotherapeutics.
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