| Literature DB >> 33539787 |
Tianzhi Huang1, Yongyong Yang1, Xiao Song1, Xuechao Wan1, Bingli Wu1, Namratha Sastry1, Craig M Horbinski2, Chang Zeng3, Deanna Tiek1, Anshika Goenka1, Fabao Liu4, Cameron W Brennan5, John A Kessler1, Roger Stupp6, Ichiro Nakano7, Erik P Sulman8, Ryo Nishikawa9, Charles David James10, Wei Zhang3, Wei Xu4, Bo Hu11, Shi-Yuan Cheng12.
Abstract
Aberrant cell proliferation is a hallmark of cancer, including glioblastoma (GBM). Here we report that protein arginine methyltransferase (PRMT) 6 activity is required for the proliferation, stem-like properties, and tumorigenicity of glioblastoma stem cells (GSCs), a subpopulation in GBM critical for malignancy. We identified a casein kinase 2 (CK2)-PRMT6-regulator of chromatin condensation 1 (RCC1) signaling axis whose activity is an important contributor to the stem-like properties and tumor biology of GSCs. CK2 phosphorylates and stabilizes PRMT6 through deubiquitylation, which promotes PRMT6 methylation of RCC1, which in turn is required for RCC1 association with chromatin and activation of RAN. Disruption of this pathway results in defects in mitosis. EPZ020411, a specific small-molecule inhibitor for PRMT6, suppresses RCC1 arginine methylation and improves the cytotoxic activity of radiotherapy against GSC brain tumor xenografts. This study identifies a CK2α-PRMT6-RCC1 signaling axis that can be therapeutically targeted in the treatment of GBM.Entities:
Keywords: CK2; GBM; GSC; PRMT; RCC1; arginine methylation; mitosis; phosphorylation; therapy response; tumorigenicity
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Year: 2021 PMID： 33539787 PMCID： PMC7979509 DOI： 10.1016/j.molcel.2021.01.015
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970