Article ID Journal Published Year Pages File Type
2112745 Cancer Letters 2014 11 Pages PDF
Abstract

•TGLI1 transcripts and encoded protein were highly expressed in approximately half of the GBM specimens we have analyzed.•TGLI1-expressing GBM xenografts grow larger and present with greater tumor angiogenesis than GLI1-expressing GBM tumors.•The heparanase-1 (HPA1) gene is a novel transcriptional target of TGLI1.•TGLI1–associated upregulation of HPA1 and VEGF-A contributes to the excessive vascularity of GBM.•The study helps define TGLI1 as a novel mediator of growth and angiogenesis of GBM.

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.

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