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Related Experiment Video

Updated: Feb 3, 2026

Using Primary Neurosphere Cultures to Study Primary Cilia
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Cilia-Associated Oxysterols Activate Smoothened.

David R Raleigh1, Navdar Sever2, Pervinder K Choksi3

  • 1Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, USA; Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.

Molecular Cell
|October 20, 2018
PubMed
Summary

Cilia-associated oxysterols activate the Hedgehog pathway by promoting Smoothened accumulation. Inhibiting oxysterol production may offer a therapeutic strategy for Hedgehog-associated cancers like medulloblastoma.

Keywords:
CBPHSD11β2HedgehogSmoothenedcilialipidmedulloblastomaoxysterolprimary ciliumsterol

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Area of Science:

  • Cellular biology
  • Molecular signaling
  • Biochemistry

Background:

  • Primary cilia are essential for transducing vertebrate Hedgehog signals.
  • The precise mechanisms of Smoothened (SMO) accumulation and activation within cilia remain unclear.

Purpose of the Study:

  • To identify factors that regulate Smoothened accumulation and activation in primary cilia.
  • To investigate the role of oxysterols in Hedgehog pathway signaling and associated cancers.

Main Methods:

  • Identification of cilia-associated oxysterols.
  • Biochemical assays to study Smoothened-oxysterol interactions.
  • Enzyme activity assays for HSD11β2.
  • Inhibition studies of oxysterol biosynthesis in cancer models.

Main Results:

  • Cilia-associated oxysterols promote Smoothened accumulation and activate the Hedgehog pathway.
  • Oxysterols bind to distinct Smoothened domains, modulating pathway activation intensity.
  • The enzyme HSD11β2 is involved in producing Smoothened-activating oxysterols.
  • Inhibition of oxysterol biosynthesis reduces oncogenic Hedgehog pathway activation and medulloblastoma growth.

Conclusions:

  • Oxysterols are key regulators of Smoothened function in primary cilia.
  • Targeting oxysterol biosynthesis presents a potential therapeutic avenue for Hedgehog-driven cancers.
  • Understanding oxysterol-Smoothened interactions is crucial for cancer therapy.