Truncated glioma-associated oncogene homolog 1 (tGLI1) (tGLI1)

Truncated glioma-associated oncogene homolog 1 (tGLI1) is an alternatively spliced, gain-of-function variant of the GLI1 transcription factor, which serves as a terminal effector of the Hedgehog signaling pathway (NIH/PubMed, 2016; NIH/PubMed, 2014). The variant arises from the deletion of 41 amino acids encoded by exon 3 and part of exon 4 of the GLI1 gene, a structural change that allows it to regulate genes not typically responsive to canonical Hedgehog signaling (Frontiers, 2018; NIH/PubMed, 2009). Unlike full-length GLI1, tGLI1 is uniquely expressed in malignant tissues such as glioblastoma and breast cancer, while remaining undetectable in normal brain and mammary cells (NIH/PubMed, 2009; AACR, 2019). It possesses the ability to activate a distinct set of target genes, including CD24, VEGF-A, and OCT4, which promote aggressive tumor phenotypes such as enhanced angiogenesis, invasion, and the maintenance of cancer stem cells (NIH/PubMed, 2019; NIH/PubMed, 2014; AACR, 2019). Furthermore, tGLI1 interacts with other oncogenic factors like STAT3 and contributes to therapeutic resistance against standard treatments, including radiation, temozolomide, and CDK4/6 inhibitors (MDPI, 2024; NIH/PubMed, 2025). Research has identified the antifungal drug ketoconazole and its derivatives as selective inhibitors that directly bind tGLI1 and antagonize its transcriptional activity, offering a potential therapeutic strategy for tGLI1-positive cancers (MDPI, 2024; AACR, 2026).

Other names

Truncated GLI1tGLI1 splice variantTruncated glioma-associated oncogene homolog 1GLI1 truncated isoform

Direct binding to the tGLI1 protein and antagonism of its transcriptional activity, leading to the downregulation of pro-tumorigenic target genes and disruption of oncogenic protein-protein interactions such as the tGLI1-STAT3 complex (MDPI, 2024; NIH/PubMed, 2025).