The GLI1 splice variant TGLI1 promotes glioblastoma angiogenesis and growth

Cancer Lett. 2014 Feb 1;343(1):51-61. doi: 10.1016/j.canlet.2013.09.014. Epub 2013 Sep 15.

Abstract

We investigated truncated glioma-associated oncogene homolog 1 (TGLI1) that behaves as gain-of-function GLI1 and promotes tumor cell migration and invasion. Herein, we report that TGLI1 had a higher propensity than GLI1 to enhance glioblastoma angiogenesis and growth, both in vivo and in vitro. TGLI1 has gained the ability to enhance expression of pro-angiogenic heparanase. In patient glioblastomas, TGLI1 levels are correlated with heparanase expression. Together, we report that TGLI1 is a novel mediator of glioblastoma angiogenesis and that heparanase is a novel transcriptional target of TGLI1, shedding new light on the molecular pathways that support tumor angiogenesis and aggressive growth.

Keywords: Angiogenesis; Cancer; GLI1; Hedgehog pathway; Transcriptional regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alternative Splicing*
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Chick Embryo
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology*
  • Glucuronidase / metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mice
  • Mice, Nude
  • Microcirculation
  • Neoplasm Transplantation
  • Neovascularization, Pathologic
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Up-Regulation
  • Zinc Finger Protein GLI1

Substances

  • GLI1 protein, human
  • Transcription Factors
  • Zinc Finger Protein GLI1
  • heparanase
  • Glucuronidase