Role of a BCL9-related β-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling
Role of a BCL9-related β-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling
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DOI：
10.1158/0008-5472.can-04-2254
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发表时间：
2004-12-01
期刊：
影响因子：
11.2
通讯作者：
Akiyama, T
中科院分区：
文献类型：
--
作者：
Adachi, S;Jigami, T;Akiyama, T
令状信号在许多发育过程和肿瘤发生中起着至关重要的作用。 P-Catenin 通过 Writ 信号传导稳定并与 TCF/LEF 转录因子家族相关，从而激活 Wnt 靶基因的转录。由腺瘤性息肉病大肠杆菌 (APC)、β-连环蛋白或 Axin 突变引起的 β-连环蛋白-TCF 介导的转录的组成型激活被认为是不同类型癌症中肿瘤发生的关键步骤。在这里，我们表明，除了 BCL9 之外，β-连环蛋白-TCF 复合物的反式激活潜力还通过与 BCL9 样蛋白 B9L 的相互作用而增强。我们发现B9L是结直肠肿瘤细胞中增强β-连环蛋白-TCF介导的转录和β-连环蛋白诱导的RK3E细胞转化所必需的。此外，相对于相应的非癌组织，B9L 的表达在约 43% 的结直肠肿瘤中异常升高。这些结果表明 B9L 在 Writ 信号传导异常激活诱导的肿瘤发生中发挥重要作用。
Writ signaling plays a crucial role in a number of developmental processes and in tumorigenesis. P-Catenin is stabilized by Writ signaling and associates with the TCF/LEF family of transcription factors, thereby activating transcription of Wnt target genes. Constitutive activation of beta-catenin-TCF-mediated transcription resulting from mutations in adenomatous polyposis coli (APC), beta-catenin, or Axin is believed to be a critical step in tumorigenesis among divergent types of cancers. Here we show that the transactivation potential of the beta-catenin-TCF complex is enhanced by its interaction with a BCL9-like protein, B9L, in addition to BCL9. We found that B9L is required for enhanced beta-catenin-TCF-mediated transcription in colorectal tumor cells and for beta-catenin-induced transformation of RK3E cells. Furthermore, expression of B9L was aberrantly elevated in about 43% of colorectal tumors, relative to the corresponding noncancerous tissues. These results suggest that B9L plays an important role in tumorigenesis induced by aberrant activation of Writ signaling.