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Orexins/hypocretins and orexin receptors in apoptosis: a mini-review

M Laburthe1, T Voisin, A El Firar

  • 1INSERM U773, Centre de Recherche Biomédicale Bichat Beaujon CRB3, Paris, France. marc.laburthe@inserm.fr

Acta Physiologica (Oxford, England)
|September 2, 2009
PubMed

Insights

Orexins trigger cancer cell death by inducing apoptosis through orexin receptors. This novel mechanism involves tyrosine phosphorylation and SHP-2 activation, offering potential cancer therapy targets.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Neuroscience

Background:

  • Neuropeptides orexins are known for regulating sleep-wake cycles.
  • Emerging research reveals orexins' role in inducing apoptosis in cancer cells.

Purpose of the Study:

  • To review recent findings on the pro-apoptotic actions of orexins.
  • To elucidate the novel mechanism of orexin receptor OX1R-mediated apoptosis.
  • To explore therapeutic potential and broader physiological roles of orexin receptors.

Main Methods:

  • Review of recent scientific literature on orexin signaling and cancer.
  • Analysis of molecular mechanisms involving orexin receptors (OX1R/OX2R) and apoptosis pathways.
  • Investigation of tyrosine phosphorylation, SHP-2 phosphatase, and mitochondrial apoptosis.

Main Results:

  • Orexins induce significant apoptosis and reduce cancer cell growth via OX1R and OX2R.
  • A novel pathway involves orexin-induced tyrosine phosphorylation of motifs in OX1R.
  • This leads to SHP-2 recruitment, activation, and subsequent cytochrome c-mediated mitochondrial apoptosis.

Conclusions:

  • Orexin receptors represent a novel therapeutic target for cancer treatment.
  • Tyrosine-based motifs in G-protein-coupled receptors (GPCRs) may have broader significance.
  • Orexin receptor-mediated apoptosis could play roles in neurodevelopment, neurodegeneration, and peripheral physiology.

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