Role of a BCL9-related beta-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

doi:10.1158/0008-5472.CAN-04-2254

Role of a BCL9-related beta-catenin-binding protein, B9L, in tumorigenesis induced by aberrant activation of Wnt signaling

Cancer Res. 2004 Dec 1;64(23):8496-501. doi: 10.1158/0008-5472.CAN-04-2254.

Authors

Shungo Adachi¹, Takafumi Jigami, Toshio Yasui, Tetsuhiro Nakano, Susumu Ohwada, Yoshihiro Omori, Sumio Sugano, Bisei Ohkawara, Hiroshi Shibuya, Tsutomu Nakamura, Tetsu Akiyama

Affiliation

¹ Institute for Molecular and Cellular Biosciences and Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

PMID: 15574752
DOI: 10.1158/0008-5472.CAN-04-2254

Abstract

Wnt signaling plays a crucial role in a number of developmental processes and in tumorigenesis. beta-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 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 Wnt signaling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Cell Transformation, Neoplastic
Colorectal Neoplasms / genetics
Colorectal Neoplasms / metabolism
Cytoskeletal Proteins / metabolism*
Cytoskeletal Proteins / physiology
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
DNA-Binding Proteins / physiology*
Humans
Immunohistochemistry
Intercellular Signaling Peptides and Proteins / physiology*
Lymphoid Enhancer-Binding Factor 1
Molecular Sequence Data
Neoplasm Proteins
Protein Binding
Rats
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / physiology
Trans-Activators / metabolism*
Trans-Activators / physiology
Transcription Factors / genetics
Transcription Factors / metabolism
Transcription Factors / physiology*
Transcription, Genetic
Transfection
Wnt Proteins
beta Catenin

Substances

BCL9L protein, human
Bcl9l protein, rat
CTNNB1 protein, human
Ctnnb1 protein, rat
Cytoskeletal Proteins
DNA-Binding Proteins
Intercellular Signaling Peptides and Proteins
Lymphoid Enhancer-Binding Factor 1
Neoplasm Proteins
Trans-Activators
Transcription Factors
Wnt Proteins
beta Catenin