Phenotypic Plasticity of Invasive Edge Glioma Stem-like Cells in Response to Ionizing Radiation

Mutsuko Minata, Alessandra Audia, Junfeng Shi, Songjian Lu, Joshua Bernstock, Marat S. Pavlyukov, Arvid Das, Sung Hak Kim, Yong Jae Shin, Yeri Lee, Harim Koo, Kirti Snigdha, Indrayani Waghmare, Xing Guo, Ahmed Mohyeldin, Daniel Gallego-Perez, Jia Wang, Dongquan Chen, Peng Cheng, Farah MukheefMinerva Contreras, Joel F. Reyes, Brian Vaillant, Erik P. Sulman, Shi Yuan Cheng, James M. Markert, Bakhos A. Tannous, Xinghua Lu, Madhuri Kango-Singh, L. James Lee, Do Hyun Nam, Ichiro Nakano*, Krishna P. Bhat


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154 引文 斯高帕斯(Scopus)


Unresectable glioblastoma (GBM) cells in the invading tumor edge can act as seeds for recurrence. The molecular and phenotypic properties of these cells remain elusive. Here, we report that the invading edge and tumor core have two distinct types of glioma stem-like cells (GSCs) that resemble proneural (PN) and mesenchymal (MES) subtypes, respectively. Upon exposure to ionizing radiation (IR), GSCs, initially enriched for a CD133 + PN signature, transition to a CD109 + MES subtype in a C/EBP-β-dependent manner. Our gene expression analysis of paired cohorts of patients with primary and recurrent GBMs identified a CD133-to-CD109 shift in tumors with an MES recurrence. Patient-derived CD133 /CD109 + cells are highly enriched with clonogenic, tumor-initiating, and radiation-resistant properties, and silencing CD109 significantly inhibits these phenotypes. We also report a conserved regulation of YAP/TAZ pathways by CD109 that could be a therapeutic target in GBM.

頁(從 - 到)1893-1905.e7
期刊Cell Reports
出版狀態Published - 12 2月 2019


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