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Published on: December 4, 2018
STMN2 is a novel target of beta-catenin/TCF-mediated transcription in human hepatoma cells
Heun-Sik Lee1, Dong Chul Lee, Mee-Hee Park
1Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-600, Republic of Korea.
Abstract:
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.
Insights
The Wnt signaling pathway
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Wnt signaling pathway, mediated by beta-catenin/TCF, is crucial in human cancers.
- Deregulation of this pathway activates genes with significant roles in tumor development.
- Identifying Wnt signaling target genes is vital for understanding beta-catenin-driven carcinogenesis.
Purpose of the Study:
- To identify novel target genes of beta-catenin-mediated transcription.
- To investigate the role of STMN2 in liver carcinogenesis.
- To elucidate the regulatory mechanism of STMN2 expression by Wnt signaling.
Main Methods:
- Gene expression analysis in liver tissues and cell lines.
- Reporter assays and chromatin immunoprecipitation (ChIP) to confirm direct transcriptional regulation.
- siRNA-mediated knockdown to assess functional significance.
Main Results:
- STMN2, a regulator of microtubule dynamics, was identified as a novel Wnt target gene.
- STMN2 expression is upregulated in hepatoma and cirrhotic liver tissues and Wnt-activated cells.
- STMN2 is a direct transcriptional target of beta-catenin/TCF, with a critical TCF binding site in its promoter.
- STMN2 is essential for the anchorage-independent growth of beta-catenin/TCF-activated hepatoma cells.
Conclusions:
- STMN2 is a direct target of beta-catenin/TCF-mediated transcription.
- STMN2 plays a significant role in promoting anchorage-independent growth in hepatoma cells.
- STMN2 emerges as a potential novel player in liver carcinogenesis driven by Wnt signaling.
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