Proteasome Inhibition Suppresses KIT-Independent Gastrointestinal Stromal Tumors Via Targeting Hippo/YAP/Cyclin D1 Signaling.

ABSTRACT: Purpose: Gastrointestinal stromal tumors (GISTs) are the most common malignant tumor of mesenchymal origin of the digestive tract. A yet more challenging resistance mechanism involves transition from oncogenic KIT to a new imatinib-insensitive oncogenic driver, heralded by loss of KIT expression. Our recent studies have shown that inhibition of cyclin D1 and Hippo signaling, which are overexpressed in KIT-independent GIST, is accompanied by anti-proliferative and apoptosis-promoting effects. PRKCQ, JUN, and the Hippo/YAP pathway coordinately regulate GIST cyclin D1 expression. Thus, targeting of these pathways could be effective therapeutically for these now untreatable tumors. Methods: Targeting cyclin D1 expression of small molecular drugs was screened by a cell monolayer g

SUBMITTER: Chen T 

PROVIDER: S-EPMC8134732 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature