Diurnal suppression of EGFR signalling by glucocorticoids and implications for tumour progression and treatment

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Mattia Lauriola1, Yehoshua Enuka2, Amit Zeisel3

  • 11] Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel [2] Unit of Histology, Embryology and Applied Biology, Department of Experimental, Diagnostic and Specialty Medicine, Bologna University, Bologna 40138, Italy.

Nature Communications
|October 4, 2014
PubMed

Insights

Glucocorticoids regulate epidermal growth factor receptor (EGFR) signaling through feedback loops, influencing the circadian clock. This discovery suggests optimizing cancer therapy timing based on circadian rhythms for improved effectiveness.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cancer Research

Background:

  • Receptor tyrosine kinases (RTKs) and nuclear receptors are crucial for homeostasis.
  • Cross-talk between RTKs and steroid hormone receptors is not well understood.
  • Glucocorticoids are known to affect various cellular processes.

Purpose of the Study:

  • To investigate the cross-talk between glucocorticoids and epidermal growth factor receptor (EGFR) signaling.
  • To elucidate the molecular mechanisms underlying glucocorticoid-mediated regulation of EGFR.
  • To explore the implications of this interaction for circadian control and cancer therapy.

Main Methods:

  • Studies in mice models.
  • Analysis of EGFR signaling pathways.
  • Investigation of feedback loops involving glucocorticoids and EGFR.
  • Assessment of cancer therapy efficacy based on treatment timing.

Main Results:

  • Glucocorticoids inhibit EGFR signaling by suppressing positive feedback and activating negative feedback loops.
  • This regulation establishes circadian control of EGFR signaling, with suppression during the active phase and enhancement during the resting phase.
  • Cancer therapy using EGFR kinase inhibitors was more effective when administered during the resting phase.

Conclusions:

  • Glucocorticoids play a significant role in the circadian regulation of EGFR signaling.
  • The findings support a paradigm for circadian clock-based cancer therapy.
  • Timing of EGFR inhibitor treatment can be optimized based on the body's natural rhythms.

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