CDX2 inhibits epithelial-mesenchymal transition in colorectal cancer by modulation of Snail expression and β-catenin stabilisation via transactivation of PTEN expression.
CDX2 inhibits epithelial-mesenchymal transition in colorectal cancer by modulation of Snail expression and β-catenin stabilisation via transactivation of PTEN expression.
复制标题
CDX2通过调节Snail的表达抑制结直肠癌上皮-间充质的转化，并通过反式激活β-catenin来稳定PTEN的表达。
DOI：
10.1038/s41416-020-01148-1
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发表时间：
2021-01
影响因子：
8.8
通讯作者：
Sun X
中科院分区：
文献类型：
--
作者：
Yu J;Li S;Xu Z;Guo J;Li X;Wu Y;Zheng J;Sun X
新出现的证据表明尾相关同源框转录因子2（CDX 2）参与各种癌症的肿瘤发生。虽然CDX 2在肿瘤侵袭和转移中发挥作用，但很少有研究关注CDX 2在大肠癌（CRC）中诱导上皮-间质转化（EMT）中的作用。进行CDX 2的免疫组织化学分析。本研究通过一系列的体内外实验来揭示CDX 2在结直肠癌侵袭和转移中的作用。CDX 2在结直肠癌组织中表达下调，CDX 2表达下调与预后不良相关。CDX 2基因的敲除可促进结肠癌细胞的体外侵袭，并通过诱导EMT表型促进体内肝转移。进一步的研究表明，CDX 2延缓Akt和GSK-3β磷酸化，从而减少Snail表达、β-连环蛋白稳定和核转位。β-连环蛋白的缺失抵消了CDX 2敲除对Slug和ZEB 1的调节。CDX 2通过调节PTEN表达拮抗CRC中的PI 3 K/Akt活性。CDX 2直接与PTEN启动子结合，反式激活其表达。我们的研究首次发现，CDX 2通过调节Snail表达和β-连环蛋白稳定化（经由PTEN表达的反式激活）来抑制EMT和CRC的转移。
Emerging evidence suggests the involvement of caudal-related homoeobox transcription factor 2 (CDX2) in tumorigenesis of various cancers. Although CDX2 functions in cancer invasion and metastasis, fewer studies focus on the role of CDX2 during the induction of epithelial–mesenchymal transition (EMT) in colorectal cancer (CRC). Immunohistochemical analysis of CDX2 was performed. A series of in vitro and in vivo experiments were conducted to reveal the role of CDX2 in the invasion and metastasis of CRC. CDX2 was downregulated in CRC tissues and reduced CDX2 correlated with poor prognosis. Knockdown of CDX2 promoted colon cancer cell invasion in vitro and facilitated liver metastasis in vivo with inducing EMT phenotypes. Further investigation indicated that CDX2 retarded Akt and GSK-3β phosphorylation, and thereby diminished Snail expression, β-catenin stabilisation and nuclear translocation. The depletion of β-catenin neutralised the regulation of Slug and ZEB1 by CDX2 knockdown. Mechanistically, CDX2 antagonised PI3K/Akt activity in CRC by modulating PTEN expression. CDX2 directly bound to the promoter of PTEN and transactivated its expression. Our study first uncovered that CDX2 inhibits EMT and metastasis of CRC by regulation of Snail expression and β-catenin stabilisation via transactivation of PTEN expression.
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DOI：
10.1158/1078-0432.ccr-09-0401
发表时间：
2009-07-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Baba Y;Nosho K;Shima K;Freed E;Irahara N;Philips J;Meyerhardt JA;Hornick JL;Shivdasani RA;Fuchs CS;Ogino S
通讯作者：
Ogino S
影响因子：
3.7
作者：
Bhat AA;Sharma A;Pope J;Krishnan M;Washington MK;Singh AB;Dhawan P
通讯作者：
Dhawan P
影响因子：
4
作者：
Jordà, M;Olmeda, D;Fabra, A
通讯作者：
Fabra, A
影响因子：
11.2
作者：
Aoki, Koji;Kakizaki, Fumihiko;Taketo, Makoto M.
通讯作者：
Taketo, Makoto M.
影响因子：
8
作者：
Gross, I.;Duluc, I.;Freund, J-N
通讯作者：
Freund, J-N