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Differential expression of hedgehog signaling components and Snail/E-cadherin in human brain tumors

Chia-Hua Chou1, Ann-Shung Lieu, Chia-Hung Wu

  • 1Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.

Oncology Reports
|September 30, 2010
PubMed

Insights

The hedgehog signaling pathway and Snail/E-cadherin are implicated in brain tumor development. Mutations in Snail impact its function, suggesting a role in tumorigenesis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Neuroscience

Background:

  • The hedgehog (Hh) signaling pathway regulates cell growth and differentiation.
  • Epithelial-mesenchymal transition (EMT), driven by Snail and E-cadherin, is crucial in tumorigenesis.
  • The roles of Hh signaling and Snail/E-cadherin in brain tumors are not fully understood.

Purpose of the Study:

  • To investigate the expression of Hh signaling components, Snail, and E-cadherin in brain tumors.
  • To identify mutations in Gli2 and Snail and their functional impact on E-cadherin regulation.
  • To elucidate the contribution of these factors to human brain tumorigenesis.

Main Methods:

  • Reverse transcription-polymerase chain reaction (RT-PCR) to analyze gene expression in 69 brain tumors.
  • RT-PCR and direct sequencing to detect mutations in Gli2 and Snail.
  • In vitro E-cadherin promoter assay to assess the functional effects of Snail mutants.

Main Results:

  • Overexpression of Hh pathway components (Smo, Ptch, Gli1, Gli2) and N-myc was observed in brain tumors.
  • Malignant brain tumors showed opposing expression of Snail and E-cadherin.
  • Sporadic Snail mutations (S96G, S111L, S111L/S119Y, Y158*) were identified, affecting E-cadherin promoter activity and nuclear translocation.

Conclusions:

  • Hedgehog signaling components, Snail expression/mutations, and E-cadherin expression are significant in human brain tumorigenesis.
  • Snail mutations alter its function, potentially contributing to tumor progression.
  • These findings highlight potential therapeutic targets in brain tumor treatment.

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