SIRT6 promotes a mesenchymal, invasive phenotype in melanoma.
- 1Department of Dermatology, University of Wisconsin, Madison, WI, USA.
- 2William S. Middleton Memorial Veterans Hospital, Madison, WI, USA.
Abstract
Melanoma is a highly aggressive cutaneous malignancy with significant metastatic potential, posing ongoing challenges in elucidating the molecular mechanisms driving its progression. Epithelial-mesenchymal transition (EMT) is a key process that enhances cancer cell migration and invasion, facilitating metastatic dissemination. Sirtuin 6 (SIRT6), a NAD⁺-dependent enzyme, has been reported to either promote or suppress EMT in a context-dependent manner; however, its function in melanoma remains poorly defined. We previously showed that SIRT6 is overexpressed in melanoma tissues and cells, where it contributes to tumor growth via an autophagy-dependent mechanism. In this study, we further investigated the role of SIRT6 in EMT using melanoma cells with stable overexpression or shRNA-mediated knockdown. Overexpression of SIRT6 enhanced cell proliferation and clonogenic survival and was associated with increased expression of mesenchymal markers and EMT-associated transcription factors. Conversely, SIRT6 knockdown significantly reduced the expression of these genes. Functionally, SIRT6 depletion markedly impaired cell migration and invasion, as demonstrated by wound-healing and Matrigel invasion assays. Collectively, these findings identify SIRT6 as a promoter of an invasive, mesenchymal phenotype in melanoma. Our results support a potential oncogenic role for SIRT6 and highlight its inhibition as a promising therapeutic strategy to limit melanoma progression and metastasis.
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BibTeX
@article{garciapeterson2026sirt6,
title = {{SIRT6 promotes a mesenchymal, invasive phenotype in melanoma.}},
author = {Liz M Garcia-Peterson and Amelia M Lemkuil and Mary A Ndiaye and Nihal Ahmad and Gagan Chhabra},
journal = {Journal of dermato-oncology},
year = {2026},
month = jul,
doi = {10.1080/29944376.2026.2700162},
url = {https://europepmc.org/article/MED/42847091},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - SIRT6 promotes a mesenchymal, invasive phenotype in melanoma.
AU - Liz M Garcia-Peterson
AU - Amelia M Lemkuil
AU - Mary A Ndiaye
AU - Nihal Ahmad
AU - Gagan Chhabra
PY - 2026
DA - 2026/07/12
JO - Journal of dermato-oncology
DO - 10.1080/29944376.2026.2700162
UR - https://europepmc.org/article/MED/42847091
AB - Melanoma is a highly aggressive cutaneous malignancy with significant metastatic potential, posing ongoing challenges in elucidating the molecular mechanisms driving its progression. Epithelial-mesenchymal transition (EMT) is a key process that enhances cancer cell migration and invasion, facilitating metastatic dissemination. Sirtuin 6 (SIRT6), a NAD⁺-dependent enzyme, has been reported to either promote or suppress EMT in a context-dependent manner; however, its function in melanoma remains poorly defined. We previously showed that SIRT6 is overexpressed in melanoma tissues and cells, where it contributes to tumor growth via an autophagy-dependent mechanism. In this study, we further investigated the role of SIRT6 in EMT using melanoma cells with stable overexpression or shRNA-mediated knockdown. Overexpression of SIRT6 enhanced cell proliferation and clonogenic survival and was associated with increased expression of mesenchymal markers and EMT-associated transcription factors. Conversely, SIRT6 knockdown significantly reduced the expression of these genes. Functionally, SIRT6 depletion markedly impaired cell migration and invasion, as demonstrated by wound-healing and Matrigel invasion assays. Collectively, these findings identify SIRT6 as a promoter of an invasive, mesenchymal phenotype in melanoma. Our results support a potential oncogenic role for SIRT6 and highlight its inhibition as a promising therapeutic strategy to limit melanoma progression and metastasis.
SN - 2994-4376
ER -