Creative Commons Non Commercial CC-BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Pancreatic ductal adenocarcinoma, often called pancreatic cancer, is one of the most aggressive and lethal malignancies. 1 Despite new therapeutic approaches including surgery, radiotherapy, and chemotherapy for pancreatic cancer have improved, pancreatic cancer remains a disease with a dismal prognosis. 2 It is characterized by a high propensity for local tumor invasion and drug resistance, but the molecular events underlying this remain mysterious. 3 Thus, investigation of the molecular mechanisms underlying pancreatic cancer development and progression is urgently needed. SIRT1, the human homolog of Sir2, is a member of sirtuins family. 4 SIRT1 is a NAD1-dependent class III deacetylase (HDAC) which plays a critical role in the regulation of critical biological processes such as metabolism, aging, oncogenesis, and cancer progression. 5,6 Emerging evidence has suggested that SIRT1 is overexpressed in some cancers, and it contributes to cell growth, drug resistance, invasion, metastasis, and recurrence; 7 however, the expression and function of SIRT1 in pancreatic cancer progression is still unclear. In this study, we sought to determine the roles of SIRT1 in pancreatic cancer development and progression. We found a key role for SIRT1 as a tumor promoter that enhances invasive and metastatic potential in pancreatic cancer in vitro. Our findings provide a new insight into the use of sirtuin inhibitors for pancreatic cancer therapy.
SIRT1 promotes the proliferation and metastasis of human pancreatic cancer cellsJianguang Jin, Zhijie Chu, Pengfei Ma, Yuanpu Meng and Yanhui Yang Abstract SIRT1 plays an important role in human malignant progression, inducing cancer cell proliferation and metastasis by regulating downstream gene expressions. However, little is known about the underlying mechanisms in which SIRT1 promotes pancreatic cancer tumorigenesis. The aim of this study is to investigate the SIRT1 expression levels and biological functions in promoting pancreatic cancer progression. We first investigated the expression of SIRT1 in a series of pancreatic cancer tissues as well as in a panel of pancreatic cancer cell lines. The effect of SIRT1 on cell activity was explored by knockdown experiments. Cell growth was measured using the MTT assay and colony-formation assay. Migration and invasion were tested using transwell assay. Our results showed that the expression of SIRT1 was significantly up-regulated both in pancreatic cancer tissues and cell lines. Knockdown of SIRT1 suppressed cell proliferation and migration of pancreatic cancer cells. This is the first report to disclo...