Therapeutic inhibition of Hedgehog-GLI signaling in cancer: epithelial, stromal, or stem cell targets?

Cancer Cell. 2008 Oct 7;14(4):281-3. doi: 10.1016/j.ccr.2008.09.007.

Abstract

Hedgehog (HH)-GLI signaling is a developmental patterning pathway used by many tumors for bulk proliferation that has been shown also to regulate cancer stem cell self-renewal and survival. Surprisingly, a recent study by Yauch et al. (2008) proposes that HH-GLI signaling acts only on the tumor stroma. The mode of action of HH-GLI signaling in cancer may shape the development of therapeutic antagonists.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Hedgehog Proteins / metabolism*
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Paracrine Communication / drug effects
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / drug effects*
  • Smoothened Receptor
  • Stromal Cells / drug effects*
  • Stromal Cells / metabolism
  • Transcription Factors / metabolism*
  • Zinc Finger Protein GLI1

Substances

  • Antineoplastic Agents
  • GLI1 protein, human
  • Hedgehog Proteins
  • Receptors, G-Protein-Coupled
  • SMO protein, human
  • Smoothened Receptor
  • Transcription Factors
  • Zinc Finger Protein GLI1