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Apoptotic Cell-Derived Extracellular Vesicles Promote Malignancy of Glioblastoma Via Intercellular Transfer of Splicing Factors.
- Source :
-
Cancer cell [Cancer Cell] 2018 Jul 09; Vol. 34 (1), pp. 119-135.e10. Date of Electronic Publication: 2018 Jun 21. - Publication Year :
- 2018
-
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.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Brain Neoplasms drug therapy
Brain Neoplasms genetics
Brain Neoplasms pathology
Cell Communication
Cell Cycle Proteins
Cell Line, Tumor
Cell Movement
Cell Proliferation
Cyclin D1 genetics
Cyclin D1 metabolism
Drug Resistance, Neoplasm
Extracellular Vesicles drug effects
Extracellular Vesicles genetics
Extracellular Vesicles pathology
Female
Glioblastoma drug therapy
Glioblastoma genetics
Glioblastoma pathology
Humans
Mice, Inbred NOD
Mice, SCID
Nuclear Proteins genetics
Nuclear Proteins metabolism
Phenotype
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins metabolism
RNA Splicing
RNA-Binding Proteins genetics
Signal Transduction
Spliceosomes drug effects
Spliceosomes genetics
Spliceosomes pathology
Tumor Burden
Apoptosis drug effects
Brain Neoplasms metabolism
Extracellular Vesicles metabolism
Glioblastoma metabolism
RNA-Binding Proteins metabolism
Spliceosomes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3686
- Volume :
- 34
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cancer cell
- Publication Type :
- Academic Journal
- Accession number :
- 29937354
- Full Text :
- https://doi.org/10.1016/j.ccell.2018.05.012