The Wnt/β-catenin/T-cell factor 4 pathway up-regulates high-mobility group A1 expression in colon cancer.
The Wnt/β-catenin/T-cell factor 4 pathway up-regulates high-mobility group A1 expression in colon cancer.
复制标题
DOI：
10.1002/cbf.2876
复制
发表时间：
2013-04
影响因子：
3.6
通讯作者：
Sumter, Takita Felder
中科院分区：
文献类型：
--
作者：
Bush, Bethany M.;Brock, Ashton T.;Deng, Jiayue A.;Nelson, Ronald A.;Sumter, Takita Felder
关键词：
高迁移率族A1（HMGA 1）编码的蛋白质在病毒整合、染色质结构修饰、肿瘤转化和转移进展中起介质作用。由于HMGA 1在大多数癌症中过表达，并且与几个Wnt应答基因具有转录关系，因此我们探索了HMGA 1在Wnt/β-catenin/TCF-4信号传导中的参与。在腺瘤性结肠息肉病（APCMin/+）小鼠，我们观察到显着上调HMGA 1 mRNA和蛋白质在肠道肿瘤相比，正常肠粘膜。相反，通过锌诱导wt-APC恢复Wnt信号传导导致HT-29细胞中HMGA 1下调。由于APC突变与β-catenin/TCF-4转录复合物的动员以及随后下游致癌靶点的激活相关，因此我们分析了HMGA 1推定的TCF-4结合元件（TBE）的5′-侧翼序列。我们在体外鉴定了两种特异性结合β-连环蛋白/TCF-4复合物的功能，并在体内鉴定了HMGA 1作为结肠癌中β-连环蛋白/TCF-4信号通路的直接靶点。总的来说，这些发现强烈暗示Wnt/β-catenin/TCF-4信号转导在调节HMGA 1中进一步扩展了受Wnt/β-catenin/TCF-4信号转导影响的广泛调节网络。
High Mobility Group A1 (HMGA1) encodes proteins that act as mediators in viral integration, modification of chromatin structure, neoplastic transformation, and metastatic progression. Because HMGA1 is overexpressed in most cancers and has transcriptional relationships with several Wnt-responsive genes, we explored the involvement of HMGA1 in Wnt/β-catenin/TCF-4 signaling. In adenomatous polyposis coli (APCMin/+) mice, we observed significant upregulation of HMGA1 mRNA and protein in intestinal tumors when compared to normal intestinal mucosa. Conversely, restoration of Wnt signaling by zinc-induction of wt-APC resulted in HMGA1 downregulation in HT-29 cells. Because APC mutations are associated with mobilization of the β-catenin/TCF-4 transcriptional complex and subsequent activation of downstream oncogenic targets, we analyzed the 5′-flanking sequence of HMGA1 putative TCF-4 binding elements (TBEs). We identified two functional that specifically bind the β-catenin/TCF-4 complex in vitro and in vivo identifying HMGA1 as an immediate target of the β-catenin/TCF-4 signaling pathway in colon cancer. Collectively, these findings strongly implicate Wnt/β-catenin/TCF-4 signaling in regulating HMGA1 to further expand the extensive regulatory network affected by Wnt/β-catenin/TCF-4 signaling.
登录
查看更多内容
影响因子：
64.5
作者：
GRODEN, J;THLIVERIS, A;WHITE, R
通讯作者：
WHITE, R
影响因子：
8
作者：
Dhar, A;Hu, J;Colburn, NH
通讯作者：
Colburn, NH
DOI：
10.1016/0027-5107(93)90027-d
发表时间：
1993-11-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
FINLAY, GJ
通讯作者：
FINLAY, GJ
影响因子：
4.8
作者：
Foster, LC;Wiesel, P;Perrella, MA
通讯作者：
Perrella, MA
影响因子：
11.2
作者：
Hillion J;Dhara S;Sumter TF;Mukherjee M;Di Cello F;Belton A;Turkson J;Jaganathan S;Cheng L;Ye Z;Jove R;Aplan P;Lin YW;Wertzler K;Reeves R;Elbahlouh O;Kowalski J;Bhattacharya R;Resar LM
通讯作者：
Resar LM