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Molecules 2018, 23(5), 1003; https://doi.org/10.3390/molecules23051003

Targeting GLI Transcription Factors in Cancer

1
Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany
2
Institute of Pharmacology and Toxicology, Goethe University, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany
3
The German Center for Lung Research, 35392 Giessen, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Takaomi Sanda
Received: 23 March 2018 / Revised: 19 April 2018 / Accepted: 20 April 2018 / Published: 24 April 2018
(This article belongs to the Special Issue Transcription Factors as Therapeutic Targets)
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Abstract

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. View Full-Text
Keywords: cancer; glioma-associated oncogene homolog; hedgehog signaling; GLI inhibitors; cancer stem cells cancer; glioma-associated oncogene homolog; hedgehog signaling; GLI inhibitors; cancer stem cells
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Didiasova, M.; Schaefer, L.; Wygrecka, M. Targeting GLI Transcription Factors in Cancer. Molecules 2018, 23, 1003.

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