STMN2 is a novel target of β-catenin/TCF-mediated transcription in human hepatoma cells

Abstract

The activity of β-catenin/TCF, the key component of Wnt signaling pathway, is frequently deregulated in human cancers, resulting in the activation of genes whose dysregulation has significant consequences on tumor development. Therefore, identifying the target genes of Wnt signaling is important for understanding β-catenin-mediated carcinogenesis. Here, we report STMN2, a gene implicated in the regulation of microtubule dynamics, as a novel target of β-catenin-mediated transcription. STMN2 was up-regulated in hepatoma and cirrhotic liver tissues compared to normal liver and also in cell lines where β-catenin/TCF is constitutively activated. Transient activation of β-catenin/TCF either by transfection of a constitutively active form of β-catenin or by LiCl treatment induced the STMN2 mRNA expression in PLC/PRF/5 cells. of the four members of STMN gene family, only STMN2 showed a Wnt-dependent expression pattern. Through promoter mapping and chromatin immunoprecipitation assays, we found that STMN2 is a direct target of β-catenin/TCF-mediated transcription and that the TCF binding site at -1713 of STMN2 promoter is critical for β-catenin/TCF-dependent expression regulation. siRNA-mediated knock-down of STMN2 expression indicated that STMN2 is required for maintaining the anchorage-independent growth state of β-catenin/TCF-activated hepatoma cells. Our results suggest that STMN2 might be a novel player of β-catenin/TCF-mediated carcinogenesis in the liver.