hrvatski

The GLI Code in Ovarian Cancer

Ovarian tumors are a heterogenic malignancy, often named “the silent killer” due to lack of symptoms, which leads to late detection of the disease. It is often diagnosed in the advanced stages when the tumor has already spread. Additional complication are the differenttissues of origin for different tumor types, or even of the same subtype. The Hedgehog signaling pathway has been implicated in ovarian tumors by several different mechanisms. Hyperactivation of the Hedgehog pathway can occur via hypermethylation of PTCH1 promoter, mutations in PTCH1 gene, microRNA activity, or through cross-talk with other signaling pathways. All these events eventually lead to activation of GLI proteins and to tilting the balance imparted by the GLI code towards activation of the pathway. Expression of GLI1 is usually associated with tumor progression in a clinical setting, but GLI2 and GLI3 also play a role by modifying the activity of GLI1 and transcription of their common transcriptional targets. In ovarian cancer, GLI3 protein is expressed in the full-length activator form, and not the shortened repressor form which is the predominant form for GLI3 protein. CRISPR/Cas9-generated knock-out ovarian cancer cell lines for each of the three GLI proteins show that all three GLI proteins are relevant for the pathway activation in ovarian cancer, including GLI3 which is usually considered a repressor.

Hedgehog-GLI signaling ; transcription factors ; GLI proteins ; GLI code ; ovarian cancer

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