The human cadherin 11 is a pro-apoptotic tumor suppressor modulating cell stemness through Wnt/β-catenin signaling and silenced in common carcinomas.
The human cadherin 11 is a pro-apoptotic tumor suppressor modulating cell stemness through Wnt/β-catenin signaling and silenced in common carcinomas.
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人钙粘蛋白 11 是一种促凋亡肿瘤抑制因子，通过 Wnt/β-连环蛋白信号传导调节细胞干性，并在常见癌症中沉默。
DOI：
10.1038/onc.2011.541
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发表时间：
2012-08-23
期刊：
影响因子：
8
通讯作者：
Tao, Q.
中科院分区：
文献类型：
--
作者：
Li, L.;Ying, J.;Li, H.;Zhang, Y.;Shu, X.;Fan, Y.;Tan, J.;Cao, Y.;Tsao, S. W.;Srivastava, G.;Chan, A. T. C.;Tao, Q.
16 q21-q22是一个6-钙粘蛋白簇的基因座，其遗传改变经常涉及多种肿瘤，提示存在关键肿瘤抑制基因（TSGs）。利用1 Mb阵列比较基因组杂交（aCGH）技术，我们在16 q21 -22.1区域发现了一个小的半合子缺失（161 Mb），其中包含一个单基因Cadherin-11（CDH 11，OB-cadherin）。CDH 11广泛表达于人正常成人和胎儿组织中，而其沉默和启动子CpG甲基化在肿瘤细胞系中频繁检测到，而在永生化的正常上皮细胞中未检测到。异常甲基化也经常在多原发肿瘤中检测到。CDH 11沉默可以通过药理学或遗传去甲基化来逆转，表明存在表观遗传机制。CDH 11的异位表达强烈抑制肿瘤的发生并诱导肿瘤细胞凋亡。此外，发现CDH 11抑制Wnt/β-catenin和AKT/Rho A信号传导，以及肌动蛋白应力纤维形成，从而进一步抑制肿瘤细胞迁移和侵袭。CDH 11还抑制上皮向间充质转化并下调干细胞标志物。因此，我们的工作鉴定了CDH 11作为功能性肿瘤抑制因子和Wnt/β-catenin和AKT/Rho A信号传导的重要拮抗剂，在常见癌中具有频繁的表观遗传失活。
Genetic alterations of 16q21-q22, the locus of a 6-cadherin cluster, are frequently involved in multiple tumors, suggesting the presence of critical tumor suppressor genes (TSGs). Using 1 Mb array comparative genomic hybridization (aCGH), we refined a small hemizygous deletion (∼1 Mb) at 16q21-22.1, which contains a single gene Cadherin-11 (CDH11, OB-cadherin). CDH11 was broadly expressed in human normal adult and fetal tissues, while its silencing and promoter CpG methylation were frequently detected in tumor cell lines, but not in immortalized normal epithelial cells. Aberrant methylation was also frequently detected in multiple primary tumors. CDH11 silencing could be reversed by pharmacologic or genetic demethylation, indicating an epigenetic mechanism. Ectopic expression of CDH11 strongly suppressed tumorigenecity and induced tumor cell apoptosis. Moreover, CDH11 was found to inhibit Wnt/β-catenin and AKT/Rho A signaling, as well as actin stress fiber formation, thus further inhibiting tumor cell migration and invasion. CDH11 also inhibited epithelial-to-mesenchymal transition and downregulated stem cell markers. Thus, our work identifies CDH11 as a functional tumor suppressor and an important antagonist of Wnt/β-catenin and AKT/Rho A signaling, with frequent epigenetic inactivation in common carcinomas.
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DOI：
10.1073/pnas.0700153104
发表时间：
2007-07-24
影响因子：
11.1
作者：
Jin, Hongchuan;Wang, Xian;Tao, Qian
通讯作者：
Tao, Qian
影响因子：
11.2
作者：
Cheng, Yingduan;Geng, Hua;Tao, Qian
通讯作者：
Tao, Qian
影响因子：
3.7
作者：
Cui Y;Ying Y;van Hasselt A;Ng KM;Yu J;Zhang Q;Jin J;Liu D;Rhim JS;Rha SY;Loyo M;Chan AT;Srivastava G;Tsao GS;Sellar GC;Sung JJ;Sidransky D;Tao Q
通讯作者：
Tao Q
影响因子：
--
作者：
Choi, Peter;Jordan, C. Diana;Chen, Chu
通讯作者：
Chen, Chu
影响因子：
5.3
作者：
Karpowicz, Phillip;Willaime-Morawek, Sandrine;van der Kooy, Derek
通讯作者：
van der Kooy, Derek