The Role of Nuclear β-Catenin Accumulation in the Twist2-Induced Ovarian Cancer EMT

Background: Twist2 has been shown to promote human tumor invasion as in breast cancer and cervical cancer. However, whether Twist2 promotes human ovarian cancer progression remains to be elucidated. Here, we investigate the role of Twist2 in ovarian cancer invasion and metastasis as well as the underlying molecular mechanisms. Methods: Twist2 expression was detected by Immunohistochemistry (IHC) on tissue microarray of human ovarian cancers with scoring procedure according to the staining intensity and pattern. Twist2 gene was stably introduced into SKOV-3 ovarian cancer cells to examine the changes of cellular morphology, motility, invasiveness, and EMT molecular markers. Results: Twist2 expression is significantly increased in ovarian cancers along with the FIGO disease stage, indicating that Twist2 may be associated with ovarian cancer metastasis. Overexpression of Twist2 induced the EMT phenotype including downregulation of E-cadherin, and upregulation of N-cadherin and beta-catenin in human ovarian cancer cells, suggesting that Twist2 might promote beta-catenin release from the E-cadherin/beta-catenin complex through inhibition of E-cadherin. Thus, beta-catenin degradation was inhibited due to inhibition of APC, and the Wnt/beta-catenin pathway was then activated by nuclear beta-catenin accumulation, which may activate transcription of downstream target genes to promote tumor invasion and metastasis. Collectively, these data indicated that beta-catenin is involved in Twist2-induced EMT in ovarian cancer. Conclusion: Our data indicates that upregulation of Twist2 is correlated with the FIGO stage in human ovarian cancers. In this report, we demonstrated that nuclear beta-catenin is accumulated in Twist2-induced EMT cells to facilitates ovarian cancer invasion and metastasis.