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.