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Targeting GLI Transcription Factors in Cancer

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...

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Detalles Bibliográficos
Autores principales: Didiasova, Miroslava, Schaefer, Liliana, Wygrecka, Malgorzata
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100584/
https://www.ncbi.nlm.nih.gov/pubmed/29695137
http://dx.doi.org/10.3390/molecules23051003
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author Didiasova, Miroslava
Schaefer, Liliana
Wygrecka, Malgorzata
author_facet Didiasova, Miroslava
Schaefer, Liliana
Wygrecka, Malgorzata
author_sort Didiasova, Miroslava
collection PubMed
description 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.
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spelling pubmed-61005842018-11-13 Targeting GLI Transcription Factors in Cancer Didiasova, Miroslava Schaefer, Liliana Wygrecka, Malgorzata Molecules Review 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. MDPI 2018-04-24 /pmc/articles/PMC6100584/ /pubmed/29695137 http://dx.doi.org/10.3390/molecules23051003 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Didiasova, Miroslava
Schaefer, Liliana
Wygrecka, Malgorzata
Targeting GLI Transcription Factors in Cancer
title Targeting GLI Transcription Factors in Cancer
title_full Targeting GLI Transcription Factors in Cancer
title_fullStr Targeting GLI Transcription Factors in Cancer
title_full_unstemmed Targeting GLI Transcription Factors in Cancer
title_short Targeting GLI Transcription Factors in Cancer
title_sort targeting gli transcription factors in cancer
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6100584/
https://www.ncbi.nlm.nih.gov/pubmed/29695137
http://dx.doi.org/10.3390/molecules23051003
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