Abstract
SIRT6 is involved in various cellular signaling pathways including those involved in tumorigenesis in association with β-catenin. However, the role of SIRT6 in tumorigenesis has been controversially reported and the studies on the role of SIRT6 in ovarian cancers is limited. In this study, we evaluated the expression and roles of SIRT6 in conjunction with the expression of active β-catenin in 104 human ovarian carcinomas and ovarian cancer cells. In human ovarian carcinomas, the expressions of SIRT6 and active β-catenin were associated with higher tumor stage, higher histologic grade, and platinum-resistance. Moreover, nuclear expression of SIRT6 (104 ovarian carcinomas; P = 0.010, 63 high-grade serous carcinomas; P = 0.040), and activated β-catenin (104 ovarian carcinomas; P = 0.013, 63 high-grade serous carcinomas; P = 0.005) were independent indicators of shorter overall survival of ovarian carcinoma patients in multivariate analysis. In OVCAR3 and OVCAR5 ovarian cancer cells, knock-down of SIRT6 significantly inhibited the migration and invasion of cells, but did not inhibit the proliferation of cells. SIRT6-mediated invasiveness of ovarian cancer cells was associated with the expression of epithelial-to-mesenchymal transition-related signaling molecules such as snail, vimentin, N-cadherin, E-cadherin, and activated β-catenin. Especially, SIRT6-mediated increase of invasiveness and activation of epithelial-to-mesenchymal transition signaling was attenuated by knock-down of β-catenin. In conclusion, this study suggests that SIRT6-β-catenin signaling is involved in the epithelial-to-mesenchymal transition of ovarian cancer cells, and the expression of SIRT6 and active β-catenin might be used as indicators of poor prognosis of ovarian carcinoma patients. In addition, our results suggest that SIRT6-β-catenin signaling might be a new therapeutic target of ovarian carcinomas.
Highlights
SIRT6 is a member of the sirtuin family and is involved in aging, metabolism, DNA damage repair, cell cycle regulation, apoptosis, and epithelial-to-mesenchymal transition (EMT) [1,2,3,4,5,6]
We evaluated the expressions of SIRT6 and active β-catenin in human ovarian carcinomas and ovarian cancer cells
There was a significant correlation between the expression of SIRT6 and active β-catenin, and their expression patterns were significantly associated with advanced clinicopathologic factors of ovarian carcinomas such as elevated serum level of CA125, higher tumor stage, and higher histologic grade
Summary
SIRT6 is a member of the sirtuin family and is involved in aging, metabolism, DNA damage repair, cell cycle regulation, apoptosis, and epithelial-to-mesenchymal transition (EMT) [1,2,3,4,5,6]. SIRT6 has been suggested as a tumor suppressor because loss of SIRT6 is associated with increased tumor formation and shorter survival of cancer patients [12, 13]. Increased expression of SIRT6 is associated with favorable prognosis of gastric and pancreatic cancer patients [14, 15]. An oncogenic role of SIRT6 has been reported in various human cancers. SIRT6 is involved in tumor progression by promoting cell cycle progression and tumor growth [16, 17], inhibiting apoptosis [18], and enhancing EMT-related invasiveness of cancer cells [19, 20]. SIRT6 expression is higher in cancer tissue compared with normal tissue in esophagus, thyroid, and melanocytes [17, 18, 21]. A careful approach and further study is needed to explore the role of SIRT6 in human cancers
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
