Apoptotic Cell-Derived Extracellular Vesicles Promote Malignancy of Glioblastoma Via Intercellular Transfer of Splicing Factors

Marat S. Pavlyukov, Hai Yu, Soniya Bastola, Mutsuko Minata, Victoria O. Shender, Yeri Lee, Suojun Zhang, Jia Wang, Svetlana Komarova, Jun Wang, Shinobu Yamaguchi, Heba Allah Alsheikh, Junfeng Shi, Dongquan Chen, Ahmed Mohyeldin, Sung Hak Kim, Yong Jae Shin, Ksenia Anufrieva, Evgeniy G. Evtushenko, Nadezhda V. AntipovaGeorgij P. Arapidi, Vadim Govorun, Nikolay B. Pestov, Mikhail I. Shakhparonov, L. James Lee, Do Hyun Nam, Ichiro Nakano*

*此作品的通信作者

研究成果: Article同行評審

207 引文 斯高帕斯(Scopus)

摘要

Aggressive cancers such as glioblastoma (GBM) contain intermingled apoptotic cells adjacent to proliferating tumor cells. Nonetheless, intercellular signaling between apoptotic and surviving cancer cells remain elusive. In this study, we demonstrate that apoptotic GBM cells paradoxically promote proliferation and therapy resistance of surviving tumor cells by secreting apoptotic extracellular vesicles (apoEVs) enriched with various components of spliceosomes. apoEVs alter RNA splicing in recipient cells, thereby promoting their therapy resistance and aggressive migratory phenotype. Mechanistically, we identified RBM11 as a representative splicing factor that is upregulated in tumors after therapy and shed in extracellular vesicles upon induction of apoptosis. Once internalized in recipient cells, exogenous RBM11 switches splicing of MDM4 and Cyclin D1 toward the expression of more oncogenic isoforms.

原文English
頁(從 - 到)119-135.e10
期刊Cancer Cell
34
發行號1
DOIs
出版狀態Published - 9 7月 2018

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