Olanzapine suppresses mPFC-norepinephrine releasing to alleviate CLOCK-induced cancer stemness under chronic stress

ABSTRACT: We identify a new mechanism by which OLZ ameliorates chronic stress-enhanced tumorigenesis and chemoresistance. OLZ reversed chronic stress-enhanced lung tumorigenesis and anxiety-like behaviors by suppressing neuro-activity in the mPFC and reducing norepinephrine (NE) releasing. To investigate the mechanism of NE in cancer stemness we performed RNA-seq of the NCI-H1299 cells under NE treatment and found that NE activated β2-adrenoceptor (ADRB2)-mediated cAMP-PKA-CREB pathway to transactivate CLOCK that further sustains cancer stemness.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268860 | GEO | 2024/08/02

REPOSITORIES: GEO