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

• Type: Article in International Scientific Journal
• Date: 2014

Authors

Lauriola, M (Author) Other; Enuka, Y (Author) Other; Zeisel, A (Author) Other; D'Uva, G (Author) Other; Roth, L (Author) Other; Sharon Sevilla, M (Author) Other; Lindzen, M (Author) Other; Sharma, K (Author) Other; Nevo, N (Author) Other; Feldman, M (Author) Other; Carvalho, S (Author) Other; Cohen Dvashi, H (Author) Other; Kedmi, M (Author) Other; Ben Chetrit, N (Author) Other; Chen, A (Author) Other; Solmi, R (Author) Other; Wiemann, S (Author) Other; Fernando Schmitt (Author) FMUP; Domany, E (Author) Other; Yarden, Y (Author) Other

Journal

Title: Nature Communications

Vol. 5

Final page: 5073

ISSN: 2041-1723

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 52 Citations

Scopus - 58 Citations

Other information

Authenticus ID: P-009-YKA

DOI: 10.1038/ncomms6073

Abstract (EN): Signal transduction by receptor tyrosine kinases (RTKs) and nuclear receptors for steroid hormones is essential for body homeostasis, but the cross-talk between these receptor families is poorly understood. We observed that glucocorticoids inhibit signalling downstream of EGFR, an RTK. The underlying mechanism entails suppression of EGFR's positive feedback loops and simultaneous triggering of negative feedback loops that normally restrain EGFR. Our studies in mice reveal that the regulation of EGFR's feedback loops by glucocorticoids translates to circadian control of EGFR signalling: EGFR signals are suppressed by high glucocorticoids during the active phase (night-time in rodents), while EGFR signals are enhanced during the resting phase. Consistent with this pattern, treatment of animals bearing EGFR-driven tumours with a specific kinase inhibitor was more effective if administered during the resting phase of the day, when glucocorticoids are low. These findings support a circadian clock-based paradigm in cancer therapy.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13