| Literature DB >> 29937354 |
Marat S Pavlyukov1, Hai Yu2, Soniya Bastola3, Mutsuko Minata3, Victoria O Shender4, Yeri Lee5, Suojun Zhang6, Jia Wang2, Svetlana Komarova3, Jun Wang3, Shinobu Yamaguchi3, Heba Allah Alsheikh3, Junfeng Shi7, Dongquan Chen8, Ahmed Mohyeldin9, Sung-Hak Kim10, Yong Jae Shin11, Ksenia Anufrieva12, Evgeniy G Evtushenko13, Nadezhda V Antipova14, Georgij P Arapidi15, Vadim Govorun4, Nikolay B Pestov16, Mikhail I Shakhparonov16, L James Lee17, Do-Hyun Nam18, Ichiro Nakano19.
Abstract
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.Entities:
Keywords: alternative splicing; apoptosis; extracellular vesicles; glioblastoma; glioma; proneural-to-mesenchymal transition; spliceosome
Mesh：
Substances：
Year: 2018 PMID： 29937354 PMCID： PMC6048596 DOI： 10.1016/j.ccell.2018.05.012
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743