The role of nuclear β-catenin accumulation in the Twist2-induced ovarian cancer EMT.
The role of nuclear β-catenin accumulation in the Twist2-induced ovarian cancer EMT.
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DOI：
10.1371/journal.pone.0078200
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Mao Y;Xu J;Li Z;Zhang N;Yin H;Liu Z
Twist2已被证明可以促进人类肿瘤的侵袭，就像在乳腺癌和宫颈癌中一样。然而，Twist2是否促进人卵巢癌的进展仍有待阐明。在这里，我们研究Twist2在卵巢癌侵袭和转移中的作用及其潜在的分子机制。采用免疫组织化学方法检测Twist2在卵巢癌组织芯片上的表达，根据染色强度和染色模式进行评分。将Twist2基因稳定导入卵巢癌细胞SKOV-3，检测细胞形态、运动能力、侵袭力及EMT分子标志物的变化。Twist2在卵巢癌中的表达随着FIGO疾病分期的增加而显著增加，提示Twist2可能与卵巢癌的转移有关。Twist2过表达诱导人卵巢癌细胞发生EMT表型，包括E-钙粘附素下调，N-钙粘附素和β-连环素上调，提示Twist2可能通过抑制E-钙粘附素促进E-钙粘附素/β-连环素复合体释放β-连环素。因此，β-连环蛋白的降解被抑制，而WNT/β-连环蛋白途径被核β-连环蛋白积聚激活，从而激活下游靶基因的转录，从而促进肿瘤的侵袭和转移。总之，这些数据表明β-连环蛋白参与了Twist2诱导的卵巢癌内胚层转移。我们的数据表明，Twist2的上调与人卵巢癌的FIGO分期有关。在这份报告中，我们证明了核β-连环蛋白在Twist2诱导的卵巢上皮细胞中积聚，从而促进卵巢癌的侵袭和转移。
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. 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. 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. 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.
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影响因子：
3.8
作者：
Haslehurst AM;Koti M;Dharsee M;Nuin P;Evans K;Geraci J;Childs T;Chen J;Li J;Weberpals J;Davey S;Squire J;Park PC;Feilotter H
通讯作者：
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8.8
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影响因子：
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作者：
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通讯作者：
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影响因子：
3.7
作者：
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通讯作者：
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