Role of a BCL9-Related β-Catenin-Binding Protein, B9L, in Tumorigenesis Induced by Aberrant Activation of Wnt Signaling

Shungo Adachi, Takafumi Jigami, Toshio Yasui, Tetsuhiro Nakano, Susumu Ohwada, Yoshihiro Omori, Sumio Sugano, Bisei Ohkawara, Hiroshi Shibuya, Tsutomu Nakamura, Tetsu Akiyama
2004 Cancer Research  
Wnt signaling plays a crucial role in a number of developmental processes and in tumorigenesis. ␤-Catenin is stabilized by Wnt signaling and associates with the TCF/LEF family of transcription factors, thereby activating transcription of Wnt target genes. Constitutive activation of ␤-catenin-TCF-mediated transcription resulting from mutations in adenomatous polyposis coli (APC), ␤-catenin, or Axin is believed to be a critical step in tumorigenesis among divergent types of cancers. Here we show
more » ... hat the transactivation potential of the ␤-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 ␤-catenin-TCFmediated transcription in colorectal tumor cells and for ␤-catenininduced 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 Wnt signaling.
doi:10.1158/0008-5472.can-04-2254 pmid:15574752 fatcat:bj4dmtb3abfklhf6iermshldie