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Molecular and Cellular Biochemistry

, Volume 450, Issue 1–2, pp 75–85 | Cite as

Probing seco-steroid inhibition of the hedgehog signaling pathway

  • Evrett N. Thompson
  • Vibhavari Sail
  • Daniel S. Raccuia
  • M. Kyle Hadden
Article
  • 140 Downloads

Abstract

Calcitriol, vitamin D3 (VD3), and structurally related VD3 analogues are inhibitors of Hh signaling in multiple contexts and are promising anti-cancer agents in Hh-dependent forms of cancer; however, the cellular mechanisms through which these compounds regulate Hh signal transmission are not clearly defined. Previous studies in this area have implicated both Smoothened, a key mediator of Hh signaling, and the vitamin D receptor (VDR) as potential mediators of Hh inhibition for this class of seco-steroids. We have performed a series of in vitro studies to more fully probe the cellular mechanisms that govern seco-steroid-mediated inhibition of Hh signaling. Our results support a role for both the Hh and VDR pathways in this process, as well as the possibility that other, as yet unidentified proteins, are also central to seco-steroid-mediated inhibition of Hh signaling.

Keywords

Vitamin D3 Calcitriol Hedgehog signaling Mouse embryonic fibroblast TGF-β 

Notes

Acknowledgements

The authors gratefully acknowledge support of this work by the American Cancer Society (RSG-13-131-01), the National Science Foundation (1515808), and the University of Connecticut Research Foundation. The Ptch−/− and Sufu−/− MEFs were a kind gift from Matthew Scott (Stanford University). The VDR−/− MEFs were a kind gift from Jun Sun (University of Illinois College of Medicine). Smo−/− MEFs were a kind gift from Philip Beachy (Stanford University).

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest in regard to the information presented in this manuscript.

Supplementary material

11010_2018_3374_MOESM1_ESM.docx (2 mb)
Supplementary material 1 (DOCX 2042 KB)

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesUniversity of ConnecticutStorrsUSA

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