Science and Research

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 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.

  • Didiasova, M.
  • Schaefer, L.
  • Wygrecka, M.

Keywords

  • Animals
  • Antineoplastic Agents/pharmacology/therapeutic use
  • Cell Transformation, Neoplastic/metabolism
  • Hedgehog Proteins/metabolism
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms/drug therapy/genetics/*metabolism
  • Neoplastic Stem Cells/drug effects/metabolism
  • Signal Transduction/drug effects
  • Transcription Factors/antagonists & inhibitors/*metabolism
  • Zinc Finger Protein GLI1/antagonists & inhibitors/*metabolism
  • GLI inhibitors
  • cancer
  • cancer stem cells
  • glioma-associated oncogene homolog
  • hedgehog signaling
Publication details
DOI: 10.3390/molecules23051003
Journal: Molecules (Basel, Switzerland)
Number: 5
Work Type: Review
Location: UGMLC
Disease Area: LC
Partner / Member: JLU
Access-Number: 29695137
See publication on PubMed

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