Coordinated targeting of CK2 and KIT in gastrointestinal stromal tumours.

ABSTRACT:

Background

Most gastrointestinal stromal tumours (GIST) are driven by activating oncogenic mutations of KIT/PDGFRA, which provide a compelling therapeutic target. Our previous studies showed that CDC37, regulated by casein kinase 2 (CK2), is a crucial HSP90 cofactor for KIT oncogenic function and a promising and more selective therapeutic target in GIST.

Methods

Biologic mechanisms of CK2-mediated CDC37 regulation were assessed in GISTs by immunoblotting, immunoprecipitations, knockdown and inactivation assays. The effects of a combination of KIT and CK2 inhibition were assessed by immunoblotting, cell viability, colony growth, cell cycle analysis, apoptosis, migration and invasiveness.

Results

CK2 overexpression was demonstrated by immunoblotting in GIST cell lines a

SUBMITTER: Huang M 

PROVIDER: S-EPMC7000686 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature