Sox4 functions as a positive regulator of beta-catenin signaling through upregulation of TCF4 during morular differentiation of endometrial carcinomas

Sox4 在子宫内膜癌胚芽分化过程中通过 TCF4 的上调发挥 β-catenin 信号传导的正调节作用

• 批准号: 23590415
• 负责人: SAEGUSA Makoto
• 金额: $ 3.33万
• 依托单位: Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590415/
• 关键词: Sox遺伝子; 細胞増殖; β-カテニン遺伝子; TCF4遺伝子; 子宮内膜癌; Sox4; Sox7; Sox9; β-カテニン; NF-κB; 子宮癌肉腫; Sox４; TCF4

In endometrial carcinoma (EmCa) cells, Sox4 could enhance beta-catenin/TCF4 transcription, through up-regulation of TCF4 at the transcription level, without any direct beta-catenin association. Cells stably overexpressing Sox4 showed significant decreases in proliferation rate, along with increases in expression of p21waf1, in contrast to increased cell growth observed with knockdown. Sox7 could transcriptionally up-regulate Sox4 expression. Finally, Sox4 immunoreactivity was frequently pronounced in morules of Em Cas, the expression being positively correlated with status of beta-catenin, TCF4, and Sox7, and inversely with cell proliferation. These data therefore suggest that Sox4 may serve as a positive regulator of beta-catenin signaling through alteration in TCF4 expression during morular differentiation of Em Ca cells, leading to inhibition of cell proliferation.

在子宫内膜癌(EmCa)细胞中，Sox4可通过在转录水平上调TCF4来增强β-catenin/TCF4的转录，而不存在任何直接的β-catenin相关性。稳定过表达Sox4的细胞表现出显著的增殖率降低，同时p21waf1的表达增加，与之相反，观察到敲除后细胞生长增加。Sox7可在转录水平上上调Sox4的表达。Sox4在子宫内膜癌中的表达与β-连环蛋白、TCF4和Sox7的表达呈正相关，与细胞增殖呈负相关。这些结果提示，Sox4可能通过改变Em Ca细胞桑丘分化过程中TCF4的表达，从而抑制细胞的增殖，从而发挥β-连环蛋白信号的正向调节作用。

项目成果

NF-κB/Sox9によるCol2A1遺伝子発現制御を介した子宮内膜癌肉腫細胞の軟骨分化誘導機構

NF-κB/Sox9调控Col2A1基因表达诱导子宫内膜癌肉瘤细胞成软骨分化的机制

• 发表时间: 2013
• 作者: 橋村美紀;三枝信;他
• 通讯作者: 他

Sox4はβ-カテニン/TCF4シグナル伝達系と協調して子宮内膜癌細胞の増殖制御・転位分化を促進する

Sox4与β-catenin/TCF4信号系统协同促进子宫内膜癌细胞的增殖控制和转移分化。

• 发表时间: 2012
• 作者: 三枝 信;橋村美紀;桑田健
• 通讯作者: 桑田健

NF-kB/Sox9によるCol2A1遺伝子発現制御を介した子宮癌肉腫細胞の軟骨分化誘導機構

NF-kB/Sox9调控Col2A1基因表达诱导子宫癌肉瘤细胞软骨分化的机制

• 作者: 橋村美紀;田雑有紀;中島裕康;原 敦子;吉田 功;三枝 信
• 通讯作者: 三枝 信

Sox4は, β-カテニン/TCF4シグナル伝達系と協調して子宮内膜癌細胞の増殖制御・転位分化を促進する

Sox4与β-catenin/TCF4信号系统协同控制子宫内膜癌细胞的增殖并促进转移分化。

• 发表时间: 2012
• 作者: 三枝信;他
• 通讯作者: 他

Transcriptional regulation of the alpha-1 type II collagen gene by nuclear factor B/p65 and Sox9 in the chondrocytic phenotype of uterine carcinosarcomas.

• DOI: 10.1016/j.humpath.2012.12.019
• 发表时间: 2013-09
• 期刊: Human pathology
• 影响因子: 3.3
• 作者: Tsutomu Yoshida;M. Hashimura;T. Kuwata;Toshihide Matsumoto;Erina Suzuki;Y. Tazo;H. Nakajima;M. Inukai;M. Saegusa