Nuclear Translocation of β-catenin is Essential for Glioma Cell Survival View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2012-12

AUTHORS

Zhendong Shi, Xiaomin Qian, Lanquan Li, Junxia Zhang, Shanjun Zhu, Jialin Zhu, Luyue Chen, Kailiang Zhang, Lei Han, Shizhu Yu, Peiyu Pu, Tao Jiang, Chunsheng Kang

ABSTRACT

Identification of molecular pathways that are essential for cancer cell survival is vital for understanding the underlying biology, as well as to design effective cancer therapeutics. β-catenin, a multifunctional oncogenic protein, participates in cell development. Its multifaceted functions primarily lie to the subcellular distribution. The present study demonstrated that β-catenin accumulated in the nucleus to a greater extent in high-grade gliomas compared with low-grade gliomas. In addition, nuclear localization correlated with a worse prognosis for patients, as determined by immunohistochemical analysis of 74 glioma samples. Nuclear expression of β-catenin was down-regulated in LN229 and U87 glioma cells by a small molecule inhibitor of β-catenin/TCF4 signaling, demonstrating strongly inhibited β-catenin/TCF4 transcriptional activity and STAT3 luciferase activity, as well as decreased mRNA and protein levels of nuclear β-catenin, TCF4, EGFR, AKT1, AKT2 and STAT3. Furthermore, repressed nuclear translocation of β-catenin resulted in inhibition of proliferation and invasiveness, and also induced apoptosis of glioma cells. Similar results were also observed in vivo; intratumoral injection of such small molecule inhibitor downregulated expression of nuclear β-catenin, TCF4, and components of the EGFR pathway, and also delayed tumor growth in nude mice harboring subcutaneous U87 xenografts. Results from the present study provided evidence that nuclear accumulation of β-catenin participated in malignant progression of gliomas and implicated poor prognosis, highlighting it as a potential therapeutic target for gliomas. More... »

PAGES

892-903

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s11481-012-9354-3

DOI

http://dx.doi.org/10.1007/s11481-012-9354-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1014180177

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22415719


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