Journal Article

Targeting GLI Transcription Factors in Cancer

Didiasova, Miroslava, Schaefer, Liliana, Wygrecka, Malgorzata

2018

Overview

Aberrant activation of hedgehog (Hh) signaling has been observed in a wide variety of tumors and accounts for more than 25% of human cancer deaths. Inhibitors targeting the Hh signal transducer Smoothened (SMO) are widely used and display a good initial efficacy in patients suffering from basal cell carcinoma (BCC); however, a large number of patients relapse. Though SMO mutations may explain acquired therapy resistance, a growing body of evidence suggests that the non-canonical, SMO-independent activation of the Hh pathway in BCC patients can also account for this adverse effect. In this review, we highlight the importance of glioma-associated oncogene (GLI) transcription factors (the main downstream effectors of the canonical and the non-canonical Hh cascade) and their putative role in the regulation of multiple oncogenic signaling pathways. Moreover, we discuss the contribution of the Hh signaling to malignant transformation and propose GLIs as central hubs in tumor signaling networks and thus attractive molecular targets in anti-cancer therapies.

• Publisher: MDPI AG,MDPI
• Subject: Animals / Antineoplastic Agents - pharmacology / Antineoplastic Agents - therapeutic use / Cancer / cancer stem cells / Cell Transformation, Neoplastic - metabolism / GLI inhibitors / glioma-associated oncogene homolog / Hedgehog Proteins - metabolism / hedgehog signaling / Humans / Kinases / Molecular Targeted Therapy / Neoplasms - drug therapy / Neoplasms - genetics / Neoplasms - metabolism / Neoplastic Stem Cells - drug effects / Neoplastic Stem Cells - metabolism / Review / Signal Transduction - drug effects / Skin cancer / Transcription factors / Transcription Factors - antagonists & inhibitors / Transcription Factors - metabolism / Zinc Finger Protein GLI1 - antagonists & inhibitors / Zinc Finger Protein GLI1 - metabolism