Il nostro articolo è su Nature Communications! Siamo felici di aver contribuito a questo ambizioso progetto internazionale sugli ormoni steroidei nello sviluppo del cancro!

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.

Vai all’articolo originale (in inglese): Mattia Lauriola, Yehoshua Enuka, Amit Zeisel, Gabriele D’Uva, Lee Roth, Michal Sharon-Sevilla, Moshit Lindzen, Kirti Sharma, Nava Nevo, Morris Feldman, Silvia Carvalho, Hadas Cohen-Dvashi, Merav Kedmi, Nir Ben-Chetrit, Alon Chen, Rossella Solmi, Stefan Wiemann, Fernando Schmitt, Eytan Domany & Yosef Yarden. Diurnal suppression of ​EGFR signalling by glucocorticoids and implications for tumour progression and treatment. Nature Communications, 2015