title: Identification of FERM domain-containing protein 5 as a novel target of β-catenin/TCF7L2 complex.
abstract: Deregulation of the canonical Wnt signaling pathway plays an important role in human tumorigenesis through the accumulation of β-catenin and subsequent transactivation of TCF7L2. Although some of the consequences associated with the accumulated β-catenin have been clarified, the comprehensive effect of activated β-catenin/TCF7L2 transcriptional complex on tumorigenesis remains to be elucidated. To understand the precise molecular mechanisms underlying colorectal cancer, we searched for genes regulated by the complex in colorectal tumors. We performed expression profile analysis of HCT116 and SW480 colon cancer cells treated with β-catenin siRNAs, and ChIP-sequencing using anti-TCF7L2 antibody. Combination of these data with public microarray data of LS174 cells with a dominant-negative form of TCF7L2 identified a total of 11 candidate genes. In this paper, we focused on FERM domain-containing protein 5 (FRMD5), and confirmed that it is regulated by both β-catenin and TCF7L2. An additional reporter assay disclosed that a region in intron1 transcriptionally regulated the expression of FRMD5. ChIP assay also corroborated that TCF7L2 associates with this region. These data suggested that FRMD5 is a novel direct target of the β-catenin/TCF7L2 complex.
authors.affiliation: Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhu
authors.affiliation: Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ohsugi
authors.affiliation: Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Terakado
authors.affiliation: Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Noguchi
authors.affiliation: Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Ikenoue
authors.affiliation: Division of Clinical Genome Research, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Furukawa
mesh_terms: D015153:Blotting, Western; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: C000594766:FRMD5 protein, human; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D025521:Tumor Suppressor Proteins; D051176:beta Catenin
keywords: Colorectal cancer; FRMD5; TCF7L2; Wnt signaling; β-catenin