PT - JOURNAL ARTICLE AU - Lo, Hui-Wen AU - Zhu, Hu AU - Cao, Xinyu AU - Aldrich, Amy AU - Ali-Osman, Francis TI - A Novel Splice Variant of <em>GLI1</em> That Promotes Glioblastoma Cell Migration and Invasion AID - 10.1158/0008-5472.CAN-09-0886 DP - 2009 Sep 01 TA - Cancer Research PG - 6790--6798 VI - 69 IP - 17 4099 - http://cancerres.aacrjournals.org/content/69/17/6790.short 4100 - http://cancerres.aacrjournals.org/content/69/17/6790.full SO - Cancer Res2009 Sep 01; 69 AB - The family of GLI zinc finger transcription factors regulates the expression of genes involved in many important cellular processes, notably embryonal development and cellular differentiation. The glioma-associated oncogene homologue 1 (GLI1) isoform, in particular, has attracted much attention because of its frequent activation in many human cancers and its interactions with other signaling pathways, such as those mediated by K-RAS, transforming growth factor-β, epidermal growth factor receptor, and protein kinase A. Here, we report the identification of a novel truncated GLI1 splice variant, tGLI1, with an in-frame deletion of 123 bases (41 codons) spanning the entire exon 3 and part of exon 4 of the GLI1 gene. Expression of tGLI1 is undetectable in normal cells but is high in glioblastoma multiforme (GBM) and other cancer cells. Although tGLI1 undergoes nuclear translocalization and transactivates GLI1-binding sites similar to GLI1, unlike GLI1, it is associated with increased motility and invasiveness of GBM cells. Using microarray analysis, we showed &gt;100 genes to be differentially expressed in tGLI1-expressing compared with GLI1-expressing GBM cells, although both cell types expressed equal levels of known GLI1-regulated genes, such as PTCH1. We further showed one of the tGLI1 up-regulated genes, CD24, an invasion-associated gene, to be required for the migratory and invasive phenotype of GBM cells. These data provide conclusive evidence for a novel gain-of-function GLI1 splice variant that promotes migration and invasiveness of GBM cells and open up a new research paradigm on the role of the GLI1 pathway in malignancy. [Cancer Res 2009;69(17):6790–8] ©2009 American Association for Cancer Research.