GLI1: A Therapeutic Target for Cancer

Frontiers in Oncology

Ruowen Zhang¹  Justin T. Avery²  Rebecca J. Boohaker² 

[1] Department of Medicine, Stony Brook University, Stony Brook, NY, United States;Oncology Department, Drug Discovery Division, Southern Research, Birmingham, AL, United States;

关键词: hedgehog;    GLI1;    therapeutic resistance;    DNA damage repair;    cancer;   

DOI  :  10.3389/fonc.2021.673154

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown