STMN2 is a novel target of beta-catenin/TCF-mediated transcription in human hepatoma cells.
The activity of beta-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 beta-catenin-mediated carcinogenesis. Here, we report STMN2, a gene implicated in the regulation of microtubule dynamics, as a novel target of beta-catenin-mediated transcription. STMN2 was up-regulated in hepatoma and cirrhotic liver tissues compared to normal liver and also in cell lines where beta-catenin/TCF is constitutively activated. Transient activation of beta-catenin/TCF either by transfection of a constitutively active form of beta-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 beta-catenin/TCF-mediated transcription and that the TCF binding site at -1713 of STMN2 promoter is critical for beta-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 beta-catenin/TCF-activated hepatoma cells. Our results suggest that STMN2 might be a novel player of beta-catenin/TCF-mediated carcinogenesis in the liver.
Lee
Heun-Sik
HS
Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-600, Republic of Korea.
Lee
Dong Chul
DC
Park
Mee-Hee
MH
Yang
Suk-Jin
SJ
Lee
Jung Ju
JJ
Kim
Dong Min
DM
Jang
Yejin
Y
Lee
Jae-Hyuck
JH
Choi
Jong Young
JY
Kang
Yun Kyung
YK
Kim
Dae Il
DI
Park
Kyung Chan
KC
Kim
Seon-Young
SY
Yoo
Hyang-Sook
HS
Choi
Eui-Ju
EJ
Yeom
Young Il
YI
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins; D008870:Microtubules / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D050777:Stathmin; D051822:T Cell Transcription Factor 1 / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism*
D008565:Membrane Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; C063314:STMN2 protein, human; D050777:Stathmin; D051822:T Cell Transcription Factor 1; D051176:beta Catenin