The sonic hedgehog-GLI1 signaling pathway in brain tumor development

Expert Opin Ther Targets. 2012 Dec;16(12):1227-38. doi: 10.1517/14728222.2012.720975. Epub 2012 Sep 19.

Abstract

Introduction: The sonic hedgehog (Shh) pathway is a regulatory network involved in development and cancer. Proteins like Ptch, SMO, and Gli are central to the Shh pathway. Other proteins like HHIP, SUFU, Bmi-1, Cyclin D2, Plakoglobin, PAX6, Nkx2.2, and SFRP1 are not so well understood in Shh regulation as Gli-1 downstream target genes.

Areas covered: In this review we try to explain the Shh pathway components and their role in development and cancer, mainly of the brain. A summary of each of the proteins is presented together with an overview of their involvement in cancer.

Expert opinion: Genetic alterations of the Shh pathway have been detected in cancer stem cells, a subgroup of tumor cells implicated in the origin and maintenance of tumors, being responsible for cancer recurrence and chemotherapy resistance. Cancer stem cells constitute a novel target for biomedical researchers. Specifically, the Shh pathway is being explored as a new opportunity for targeted therapies against tumors. Therefore, a better knowledge of every of the regulators of the Shh pathway is needed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain Neoplasms / metabolism*
  • Hedgehog Proteins / metabolism*
  • Homeobox Protein Nkx-2.2
  • Homeodomain Proteins
  • Humans
  • Nuclear Proteins
  • Signal Transduction
  • Transcription Factors / metabolism*
  • Zinc Finger Protein GLI1

Substances

  • GLI1 protein, human
  • Hedgehog Proteins
  • Homeobox Protein Nkx-2.2
  • Homeodomain Proteins
  • NKX2-2 protein, human
  • Nuclear Proteins
  • Transcription Factors
  • Zinc Finger Protein GLI1