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Related Concept Videos

Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Chromatin Modification in iPS Cells01:32

Chromatin Modification in iPS Cells

Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids01:21

Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids

Glucocorticoids, a class of anti-inflammatory drugs, are pivotal in treating moderate to severe Crohn's disease by inducing remission. They exhibit their anti-inflammatory action by inhibiting the production of inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, and chemokines like IL-8. In addition, they reduce the expression of inflammatory cell adhesion molecules and inhibit gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2 (COX-2),...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

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Quantitative PCR-based Assay to Measure Sonic Hedgehog Signaling in Cellular Model of Ciliogenesis
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Glucocorticoid compounds modify smoothened localization and hedgehog pathway activity.

Yu Wang1, Lance Davidow, Anthony C Arvanites

  • 1Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.

Chemistry & Biology
|August 28, 2012
PubMed
Summary

Glucocorticoids modulate Smo ciliary accumulation in the Hedgehog pathway. This offers potential treatments for drug-resistant cancers but also raises concerns about unintended drug effects.

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Published on: December 14, 2015

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Pharmacology

Background:

  • The Hedgehog signaling pathway is implicated in various cancers.
  • Smoothened (Smo), a key protein in this pathway, is a primary drug target.
  • Smo's localization to the primary cilium is crucial for pathway activation.

Purpose of the Study:

  • To identify modulators of Smo ciliary accumulation.
  • To investigate novel therapeutic strategies for Smo-driven cancers, including drug-resistant forms.

Main Methods:

  • High-content screening of glucocorticoids for their effect on Smo localization.
  • Testing glucocorticoids against wild-type and mutant Smo proteins (SmoM2, SmoD473H).

Main Results:

  • Certain glucocorticoids promote Smo accumulation, increasing sensitivity to Hedgehog signaling.
  • Other glucocorticoids inhibit Smo ciliary localization and signaling for both wild-type and resistant Smo mutants.
  • These inhibitors are effective against Smo mutants resistant to known antagonists.

Conclusions:

  • Glucocorticoids can pharmacologically modulate Smo signaling, offering a new avenue for treating drug-resistant Smo mutations in cancer.
  • Potential for glucocorticoid-based therapies targeting resistant Smo forms.
  • Caution is advised regarding potential off-target effects of glucocorticoids on the Hedgehog pathway.