ArticleBMC cancer2013
High SIRT1 expression is a negative prognosticator in pancreatic ductal adenocarcinoma.
Article in BMC cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Survival and Clinicopathological Significance of SIRT1 Expression in Cancers: A Meta-Analysis.Frontiers in endocrinology · 2019Pooled it
- SIRT1 Promotes Breast Cancer Stem Cell-Associated Properties and Represents a Potential Therapeutic Target.International journal of molecular sciences · 2026Article
- Review
- Sirtuins as Key Regulators in Pancreatic Cancer: Insights into Signaling Mechanisms and Therapeutic Implications.Cancers · 2024Review
- Gemcitabine therapeutically disrupts essential SIRT1-mediated p53 repression in atypical teratoid/rhabdoid tumors.Cell reports. Medicine · 2024Article
- A novel pyroptosis-associated lncRNA LINC01133 promotes pancreatic adenocarcinoma development via miR-30b-5p/SIRT1 axis.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- miRNA Expression May Have Implications for Immunotherapy in PDGFRA Mutant GISTs.International journal of molecular sciences · 2022Article
- Additive pharmacological interaction between sirtuin inhibitor cambinol and paclitaxel in MCF7 luminal and MDA-MB-231 triple-negative breast cancer cells.Pharmacological reports : PR · 2022Article
- Antagonistic Pharmacological Interaction between Sirtuin Inhibitor Cambinol and Paclitaxel in Triple-Negative Breast Cancer Cell Lines: An Isobolographic Analysis.International journal of molecular sciences · 2022Article
- SYT8 promotes pancreatic cancer progression via the TNNI2/ERRα/SIRT1 signaling pathway.Cell death discovery · 2021Article
- SIRT1 coordinates with the CRL4B complex to regulate pancreatic cancer stem cells to promote tumorigenesis.Cell death and differentiation · 2021Article
- Recent advances of SIRT1 and implications in chemotherapeutics resistance in cancer.American journal of cancer research · 2021Review
- Circadian Genes as Therapeutic Targets in Pancreatic Cancer.Frontiers in endocrinology · 2020Review
- Article
- Article
- Meta-analysis of SIRT1 expression as a prognostic marker for overall survival in gastrointestinal cancer.Oncotarget · 2017Article
- Article
- SIRT1 Regulates the Chemoresistance and Invasiveness of Ovarian Carcinoma Cells.Translational oncology · 2017Article
- Pancreatic Cancer, A Mis-interpreter of the Epigenetic Language.The Yale journal of biology and medicine · 2016Review
- Sirtuin 1 stimulates the proliferation and the expression of glycolysis genes in pancreatic neoplastic lesions.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSeveral lines of evidence indicate that Sirt1, a class III histone deacetylase (HDAC) is implicated in the initiation and progression of malignancies and thus gained attraction as druggable target. Since data on the role of Sirt1 in pancreatic ductal adenocarcinoma (PDAC) are sparse, we investigated the expression profile and prognostic significance of Sirt1 in vivo as well as cellular effects of Sirt1 inhibition in vitro.
methodsSirt1 expression was analyzed by immunohistochemistry in a large cohort of PDACs and correlated with clinicopathological and survival data. Furthermore, we investigated the impact of overexpression and small molecule inhibition on Sirt1 in pancreatic cancer cell culture models including combinatorial treatment with chemotherapy and EGFR-inhibition. Cellular events were measured quantitatively in real time and corroborated by conventional readouts including FACS analysis and MTT assays.
resultsWe detected nuclear Sirt1 expression in 36 (27.9%) of 129 PDACs. SIRT1 expression was significantly higher in poorly differentiated carcinomas. Strong SIRT1 expression was a significant predictor of poor survival both in univariate (p = 0.002) and multivariate (HR 1.65, p = 0.045) analysis. Accordingly, overexpression of Sirt1 led to increased cell viability, while small molecule inhibition led to a growth arrest in pancreatic cancer cells and impaired cell survival. This effect was even more pronounced in combinatorial regimens with gefitinib, but not in combination with gemcitabine.
conclusionsSirt1 is an independent prognosticator in PDACs and plays an important role in pancreatic cancer cell growth, which can be levered out by small molecule inhibition. Our data warrant further studies on SIRT1 as a novel chemotherapeutic target in PDAC.
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