LEF1 regulates glioblastoma cell proliferation, migration, invasion, and cancer stem-like cell self-renewal
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Glioblastoma multiforme (GBM; WHO grade IV) is one of the most common primary tumors of the central nervous system. This disease remains one of the incurable human malignancies because the molecular mechanism driving the GBM development and recurrence is still largely unknown. Here, we show that knockdown of lymphocyte enhancer factor-1 (LEF1), a major transcription factor of Wnt pathway, inhibits U251 cell migration, invasion, and proliferation. Furthermore, downregulation of LEF1 expression inhibits the self-renewal capacity of U251 GBM stem-like cells and decreases the expression level of the GBM stem-like cell (GSC) markers such as CD133 and nestin. Our findings reveal that LEF1 maintains the GBM cell proliferation, migration, and GBM stem-like cell self-renewal. Taken together, these results suggest that LEF1 may be a novel therapeutic target for GBM suppression.
KeywordsGlioblastoma multiforme LEF1 Proliferation Invasion Stemness
This work is supported by the Project Supported by the Natural Science Basic Research Plan in Shaanxi Province of China (Program No. 2013JQ3017), National Natural Science Foundation of China (No. 81272801 and No. 81271290), National Key Basic Research Program of China (“973” Project) (2010CB933900), scientific research program funded by Shaanxi Provincial Health Department (Program No. 2014D21 and 2014D24), Scientific Research Program Funded by Shaanxi Provincial Education Department (Program No. 14JK1617), and Program for Youth Science and Technology Star of Shaanxi Province (2014KJXX-76).
Conflicts of interest
- 7.Gao X, Jin W (2014) The emerging role of tumor-suppressive microRNA-218 in targeting glioblastoma stemness. Cancer LettGoogle Scholar
- 18.Conacci-Sorrell ME, Ben-Yedidia T, Shtutman M, Feinstein E, Einat P, Ben-Ze’ev A. Nr-cam is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis. Genes Dev. 2002;16:2058–72.PubMedCentralPubMedCrossRefGoogle Scholar
- 23.Zhang X, Zhao M, Huang AY, Fei Z, Zhang W, Wang XL. The effect of cyclin D expression on cell proliferation in human gliomas. J Clin Neurosci Off J Neurosurg Soc Australas. 2005;12:166–8.Google Scholar