Liz M Garcia-Peterson, Amelia M Lemkuil, Mary A Ndiaye, Nihal Ahmad, Gagan Chhabra
{"title":"SIRT6 promotes a mesenchymal, invasive phenotype in melanoma.","authors":"Liz M Garcia-Peterson, Amelia M Lemkuil, Mary A Ndiaye, Nihal Ahmad, Gagan Chhabra","doi":"10.1080/29944376.2026.2700162","DOIUrl":"10.1080/29944376.2026.2700162","url":null,"abstract":"<p><p>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<sup>+</sup>-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.</p>","PeriodicalId":521256,"journal":{"name":"Journal of dermato-oncology","volume":"2 1","pages":"2700162"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Karla B Anaya Aldrete, Mary A Ndiaye, Glorimar Guzmán-Pérez, Gabriella R Zaemisch, Chandra K Singh, Gagan Chhabra, Nihal Ahmad
{"title":"Mechanistic and preclinical evaluation of SIRT3 as a therapeutic target in melanoma.","authors":"Karla B Anaya Aldrete, Mary A Ndiaye, Glorimar Guzmán-Pérez, Gabriella R Zaemisch, Chandra K Singh, Gagan Chhabra, Nihal Ahmad","doi":"10.1080/29944376.2026.2656032","DOIUrl":"10.1080/29944376.2026.2656032","url":null,"abstract":"<p><p>Despite advances in targeted inhibitors and immunotherapies, melanoma remains one of the deadliest skin cancers due to high metastatic potential and resistance to current therapies. This underscores a critical need for new, mechanism-based treatment strategies. Sirtuins, a family of class III histone deacetylases, have been implicated by our lab and others in numerous cellular functions, diseases, and cancers including melanoma. Here, we sought to extend our findings on the pro-proliferative role of SIRT3 by: (i) defining downstream mechanisms using PCR array and NanoString gene-expression profiling on CRISPR/Cas9-mediated SIRT3 knockout (KO) in melanoma cells; (ii) assessing effects of siRNA against SIRT3 in patient-derived xenograft (PDX) and Braf<sup>V600E</sup>/Pten<sup>NULL</sup> melanoma models; and (iii) evaluating efficacy of SIRT3 inhibitor 4'-Bromo-resveratrol (4'-BR) in PDXes. SIRT3 KO significantly reduced growth and colony formation in A375 and G361 melanoma cells. PCR array and NanoString analysis revealed modulation of key cancer-related signaling molecules. <i>In vivo</i>, siRNA-mediated SIRT3 inhibition in melanoma PDXes and Braf<sup>V600E</sup>/Pten<sup>NULL</sup> mice trended toward reduced tumor growth. However, dual SIRT1/SIRT3 inhibition with 4'-BR (50 mg/kg, <i>ip</i>, 2x/week) significantly decreased tumor volume and weight in melanoma PDXes. Overall, our data suggests that targeting SIRT1 and SIRT3 together could offer greater therapeutic benefit and should be validated and optimized.</p>","PeriodicalId":521256,"journal":{"name":"Journal of dermato-oncology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13178468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147966753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Blue light and ultraviolet radiation: comparative biophysical properties and their roles in skin carcinogenesis and photoaging.","authors":"Robert L McKay, Shiyong Wu","doi":"10.1080/29944376.2025.2595383","DOIUrl":"10.1080/29944376.2025.2595383","url":null,"abstract":"<p><p>Ultraviolet radiation (UVR), especially UVB and UVA, drives photoaging and carcinogenesis, whereas blue light (BL, 400-500 nm) remains less studied. Evidence shows BL induces melanogenesis, generates reactive oxygen species, impairs deoxyribonucleic acid (DNA) repair, and accelerates pigmentation and oxidative stress. Though not directly linked to skin cancer, BL amplifies UVR damage and hastens photoaging, yet also suppresses tumor growth by promoting apoptosis, revealing dual context-dependent effects. This review highlights BL's biological and clinical relevance, phototype-dependent responses, and mechanistic uncertainties. Expanding photoprotection beyond UVR to include BL is essential for comprehensive, evidence-based strategies safeguarding skin health across diverse populations.</p>","PeriodicalId":521256,"journal":{"name":"Journal of dermato-oncology","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12903870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146204727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Liquid Biopsy for Cutaneous Melanoma: Opportunities and Challenges in Detecting and Characterizing Circulating Tumor Cells.","authors":"Weizheng Wang, Rylee Rickett, Sireesh Teertam, Sundaram Gunasekaran, Vijayasaradhi Setaluri","doi":"10.1080/29944376.2025.2578127","DOIUrl":"10.1080/29944376.2025.2578127","url":null,"abstract":"<p><p>Advances in techniques to identify and enumerate circulating tumor cells (CTC) in the peripheral blood of patients with cancer have made liquid biopsy a promising tool. However, detecting CTC as prognostic markers for the risk of recurrence in patients diagnosed with primary cancer remains challenging. The currently available methods have many limitations, specifically the lack of selectivity. Novel approaches and sensors that leverage melanoma cell surface markers and improve the specific detection of intact melanoma cells in blood are needed. Refinements in biosensor development and multiplexed microfluidic platforms are poised to make point-of-care devices for the better management of melanoma.</p>","PeriodicalId":521256,"journal":{"name":"Journal of dermato-oncology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148202135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}