Hyperphosphorylation of CDH1 in Glioblastoma Cancer Stem Cells Attenuates APC/C^CDH1 Activity and Pharmacologic Inhibition of APC/C^CDH1/CDC20 Compromises Viability.

ABSTRACT: Glioblastoma (GBM) is the most common and lethal primary brain tumor and remains incurable. This is in part due to the cellular heterogeneity within these tumors, which includes a subpopulation of treatment-resistant cells called cancer stem-like cells (CSC). We previously identified that the anaphase-promoting complex/cylosome (APC/C), a key cell-cycle regulator and tumor suppressor, had attenuated ligase activity in CSCs. Here, we assessed the mechanism of reduced activity, as well as the efficacy of pharmacologically targeting the APC/C in CSCs. We identified hyperphosphorylation of CDH1, but not pseudosubstrate inhibition by early mitotic inhibitor 1 (EMI1), as a major mechanism driving attenuated APC/C^CDH1 activity in the G₁-phase of the cell cycle in CSCs. Small

SUBMITTER: De K 

PROVIDER: S-EPMC7271747 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature