The glucocorticoid receptor associates with RAS complexes to inhibit cell proliferation and tumor growth
Menée à l'aide de fibroblastes embryonnaires de souris, d'une lignée cellulaire de cancer du poumon d'origine humaine et de xénogreffes sur un modèle murin, cette étude met en évidence un mécanisme par lequel le récepteur des glucocorticoïdes, en interagissant avec les complexes protéiques RAS, inhibe la prolifération cellulaire et la croissance tumorale
The glucocorticoid receptor (GR) is a nuclear hormone receptor that localizes to the cytoplasm in the absence of activating ligands. Caratti et al. found that GR interacted with cytoplasmic complexes containing the small GTPase RAS and the RAS-activating kinase RAF1 in mouse embryonic fibroblasts and human lung cancer A549 cells. The genetic loss of GR or the ligand-induced nuclear translocation of GR increased the activation of RAS and RAS-dependent mitogenic signaling, stimulated cell proliferation in vitro, and promoted the growth of A549 xenografts in mice. These effects on RAS activation did not depend on GR transcriptional activity. Thus, in addition to controlling transcriptional programs that regulate cell growth, GR also limits the activation of RAS through a nongenomic mechanism.
Science Signaling 2022