Targeting the hedgehog transcription factors GLI1 and GLI2 restores sensitivity to vemurafenib-resistant human melanoma cells

@article{FaioFlores2017TargetingTH,
  title={Targeting the hedgehog transcription factors GLI1 and GLI2 restores sensitivity to vemurafenib-resistant human melanoma cells},
  author={Fernanda Fai{\~a}o-Flores and D{\'e}bora Kristina Alves-Fernandes and Paula Comune Pennacchi and Silvana Sandri and Anna Luiza Silva Almeida Vicente and Cristovam Scapulatempo-Neto and Vinicius de Lima Vazquez and Rui Manuel Reis and Jagat Singh Chauhan and Colin Ronald Goding and Keiran S. M. Smalley and Silvia Stuchi Maria-Engler},
  journal={Oncogene},
  year={2017},
  volume={36},
  pages={1849 - 1861}
}
BRAF inhibitor (BRAFi) therapy for melanoma patients harboring the V600E mutation is initially highly effective, but almost all patients relapse within a few months. Understanding the molecular mechanisms underpinning BRAFi-based therapy is therefore an important issue. Here we identified a previously unsuspected mechanism of BRAFi resistance driven by elevated Hedgehog (Hh) pathway activation that is observed in a cohort of melanoma patients after vemurafenib treatment. Specifically, we… 
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TLDR
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Up-regulation of GLI1 in vincristine-resistant rhabdomyosarcoma and Ewing sarcoma
TLDR
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Oncogenic GLI1 and STAT1/3 activation drives immunosuppressive tryptophan/kynurenine metabolism via synergistic induction of IDO1 in skin cancer cells
TLDR
The immunosuppressive IDO1-kynurenine pathway is identified as a novel pro-tumorigenic effector of oncogenic HH-IL6 and GLI-STAT cooperation and suggests simultaneous pharmacological targeting of the HH/GLI, JAK/STAT and IDO 1- kynurenines axis as rational combination therapy in skin cancers.
The Role of Smoothened-Dependent and -Independent Hedgehog Signaling Pathway in Tumorigenesis
TLDR
This review describes the various SMO-dependent andSMO-independent routes of GLI regulation in the tumorigenesis of multiple cancers in order to provide a holistic view of the paradigms of hedgehog signaling networks involvingGLI regulation.
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