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 β-catenin in human ovarian cancer cells, suggesting that Twist2 might promote β-catenin release from the E-cadherin/β-catenin complex through inhibition of E-cadherin. Thus, β-catenin degradation was inhibited due to inhibition of APC, and the Wnt/β-catenin pathway was then activated by nuclear β-catenin accumulation, which may activate transcription of downstream target genes to promote tumor invasion and metastasis. Collectively, these data indicated that β-catenin is involved in Twist2-induced EMT in ovarian cancer.


CONCLUSIONS
Our data indicates that upregulation of Twist2 is correlated with the FIGO stage in human ovarian cancers. In this report, we demonstrated that nuclear β-catenin is accumulated in Twist2-induced EMT cells to facilitates ovarian cancer invasion and metastasis.
Department of Pathophysiology in Basic Science, Medical College of Xiamen University, Xiamen, Fujian, China.
Yubin
Y
Mao
Jinfei
J
Xu
Zhihan
Z
Li
Nini
N
Zhang
Hao
H
Yin
Zuguo
Z
Liu
D021581:Active Transport, Cell Nucleus / Q000235:genetics; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D015820:Cadherins; D012097:Repressor Proteins; C486274:TWIST2 protein, human; D051879:Twist-Related Protein 1; D051176:beta Catenin