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Review
. 2021 May 25:11:673154.
doi: 10.3389/fonc.2021.673154. eCollection 2021.

GLI1: A Therapeutic Target for Cancer

Justin T Avery  1 , Ruowen Zhang  2 , Rebecca J Boohaker  1
Affiliations
Review

GLI1: A Therapeutic Target for Cancer

Justin T Avery et al. Front Oncol. .

Abstract

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.

Keywords: DNA damage repair; GLI1; cancer; hedgehog; therapeutic resistance.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Canonical and Non-canonical activation of GLI1. Compounds originally designed to inhibit the Hedgehog pathway focused on canonical regulators, like SMO, but were found to be ineffective in some cancers due to non-canonical activation. Aberrant activation of GLI1 promotes DNA damage repair, invasion/metastasis, proliferation, and therapeutic resistance through transcriptional regulation of target genes.
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References

    1. Kumar S, Balczarek KA, Lai ZC. Evolution of the Hedgehog Gene Family. Genetics (1996) 142(3):965–72. 10.1093/genetics/142.3.965 - DOI - PMC - PubMed
    1. McMahon AP. More Surprises in the Hedgehog Signaling Pathway. Cell (2000) 100(2):185–8. 10.1016/s0092-8674(00)81555-x - DOI - PubMed
    1. Ingham PW, Nakano Y, Seger C. Mechanisms and Functions of Hedgehog Signalling Across the Metazoa. Nat Rev Genet (2011) 12(6):393–406. 10.1038/nrg2984 - DOI - PubMed
    1. Mohler J. Requirements for Hedgehog, a Segmental Polarity Gene, in Patterning Larval and Adult Cuticle of Drosophila. Genetics (1988) 120(4):1061–72. 10.1093/genetics/120.4.1061 - DOI - PMC - PubMed
    1. Belloni E, Muenke M, Roessler E, Traverso G, Siegel-Bartelt J, Frumkin A, et al. . Identification of Sonic Hedgehog as a Candidate Gene Responsible for Holoprosencephaly. Nat Genet (1996) 14(3):353–6. 10.1038/ng1196-353 - DOI - PubMed