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GLI1: A Therapeutic Target for Cancer
GLI1 is a transcriptional effector at the terminal end of the Hedgehog signaling (Hh) pathway and is tightly regulated during embryonic development and tissue patterning/differentiation. GLI1 has low-level expression in differentiated tissues, however, in certain cancers, aberrant activation of GLI1...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186314/ https://www.ncbi.nlm.nih.gov/pubmed/34113570 http://dx.doi.org/10.3389/fonc.2021.673154 |
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author | Avery, Justin T. Zhang, Ruowen Boohaker, Rebecca J. |
author_facet | Avery, Justin T. Zhang, Ruowen Boohaker, Rebecca J. |
author_sort | Avery, Justin T. |
collection | PubMed |
description | GLI1 is a transcriptional effector at the terminal end of the Hedgehog signaling (Hh) pathway and is tightly regulated during embryonic development and tissue patterning/differentiation. GLI1 has low-level expression in differentiated tissues, however, in certain cancers, aberrant activation of GLI1 has been linked to the promotion of numerous hallmarks of cancer, such as proliferation, survival, angiogenesis, metastasis, metabolic rewiring, and chemotherapeutic resistance. All of these are driven, in part, by GLI1’s role in regulating cell cycle, DNA replication and DNA damage repair processes. The consequences of GLI1 oncogenic activity, specifically the activity surrounding DNA damage repair proteins, such as NBS1, and cell cycle proteins, such as CDK1, can be linked to tumorigenesis and chemoresistance. Therefore, understanding the underlying mechanisms driving GLI1 dysregulation can provide prognostic and diagnostic biomarkers to identify a patient population that would derive therapeutic benefit from either direct inhibition of GLI1 or targeted therapy towards proteins downstream of GLI1 regulation. |
format | Online Article Text |
id | pubmed-8186314 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81863142021-06-09 GLI1: A Therapeutic Target for Cancer Avery, Justin T. Zhang, Ruowen Boohaker, Rebecca J. Front Oncol Oncology GLI1 is a transcriptional effector at the terminal end of the Hedgehog signaling (Hh) pathway and is tightly regulated during embryonic development and tissue patterning/differentiation. GLI1 has low-level expression in differentiated tissues, however, in certain cancers, aberrant activation of GLI1 has been linked to the promotion of numerous hallmarks of cancer, such as proliferation, survival, angiogenesis, metastasis, metabolic rewiring, and chemotherapeutic resistance. All of these are driven, in part, by GLI1’s role in regulating cell cycle, DNA replication and DNA damage repair processes. The consequences of GLI1 oncogenic activity, specifically the activity surrounding DNA damage repair proteins, such as NBS1, and cell cycle proteins, such as CDK1, can be linked to tumorigenesis and chemoresistance. Therefore, understanding the underlying mechanisms driving GLI1 dysregulation can provide prognostic and diagnostic biomarkers to identify a patient population that would derive therapeutic benefit from either direct inhibition of GLI1 or targeted therapy towards proteins downstream of GLI1 regulation. Frontiers Media S.A. 2021-05-25 /pmc/articles/PMC8186314/ /pubmed/34113570 http://dx.doi.org/10.3389/fonc.2021.673154 Text en Copyright © 2021 Avery, Zhang and Boohaker https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Avery, Justin T. Zhang, Ruowen Boohaker, Rebecca J. GLI1: A Therapeutic Target for Cancer |
title | GLI1: A Therapeutic Target for Cancer |
title_full | GLI1: A Therapeutic Target for Cancer |
title_fullStr | GLI1: A Therapeutic Target for Cancer |
title_full_unstemmed | GLI1: A Therapeutic Target for Cancer |
title_short | GLI1: A Therapeutic Target for Cancer |
title_sort | gli1: a therapeutic target for cancer |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186314/ https://www.ncbi.nlm.nih.gov/pubmed/34113570 http://dx.doi.org/10.3389/fonc.2021.673154 |
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