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

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 ß2-adrenoceptor (ADRB2)-mediated cAMP-PKA-CREB pathway to transactivate CLOCK that further sustains cancer stemness. Overall design: We then performed gene expression profiling analysis using data obtained from RNA-seq of NCI-H1299 cells under norepinephrine treatment. Comparative gene expression profiling analysis of RNA-seq data for NCI-H1299 treated with DMSO or norepinephrine.