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A novel function of the human oncogene Stil: Regulation of PC12 cell toxic susceptibility through the Shh pathway

Lei Li1, Aprell L Carr1, Lei Sun2

  • 1Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556.

Scientific Reports
|November 10, 2015
PubMed

Insights

The human oncogene Stil regulates toxic susceptibility in dopaminergic neurons. Stil

Area of Science:

  • Neuroscience
  • Oncology
  • Cell Biology

Background:

  • The human oncogene SCL/TAL1 interrupting locus (Stil) is crucial in vertebrate development.
  • Its role in neural toxic susceptibility remains largely unexplored.

Purpose of the Study:

  • To investigate the function of Stil in regulating toxic susceptibility in mammalian dopaminergic (DA)-like PC12 cells.
  • To elucidate the signaling pathways involved in Stil-mediated regulation of cellular response to toxins.

Main Methods:

  • RNAi-mediated knockdown and overexpression of Stil in PC12 cells.
  • Assessment of cell survival following toxic drug treatment in proliferating and differentiated PC12 cells.
  • Modulation of Sonic hedgehog (Shh) signaling to investigate its interaction with Stil.

Main Results:

  • Stil knockdown increased cell death in differentiated neurons upon toxic drug exposure.
  • Stil overexpression enhanced toxic susceptibility in proliferating PC12 cells but not in differentiated neurons.
  • Manipulation of Shh signaling mimicked Stil's effects, indicating its involvement in the pathway.

Conclusions:

  • The human oncogene Stil plays a novel role in modulating neural toxic susceptibility.
  • Stil exerts its regulatory function through the Sonic hedgehog (Shh) signaling pathway.
  • These findings offer new insights into the mechanisms underlying neuronal vulnerability to toxins.

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