LEF1 regulates glioblastoma cell proliferation, migration, invasion, and cancer stem-like cell self-renewal

Tumour Biol. 2014 Nov;35(11):11505-11. doi: 10.1007/s13277-014-2466-z. Epub 2014 Aug 16.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Blotting, Western
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Cell Movement*
  • Cell Proliferation*
  • Fluorescent Antibody Technique
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Humans
  • Immunoenzyme Techniques
  • Lymphoid Enhancer-Binding Factor 1 / antagonists & inhibitors
  • Lymphoid Enhancer-Binding Factor 1 / genetics
  • Lymphoid Enhancer-Binding Factor 1 / metabolism*
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Wound Healing

Substances

  • LEF1 protein, human
  • Lymphoid Enhancer-Binding Factor 1
  • RNA, Messenger
  • RNA, Small Interfering