Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is associated with stem-like cancer cell functions in pediatric high-grade glioma

Pediatric high-grade gliomas represent 8-12% of all primary tumors of the nervous system in children. Five-year survival for these pediatric aggressive tumors is poor (15-35%) indicating the need to develop better treatments for pediatric high-grade gliomas. In this work we used SF188 and SJ-GBM2 ce...

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Bibliographic Details
Published in:PloS one 2017-05, Vol.12 (5), p.e0176879-e0176879
Main Authors: Sanchez-Diaz, Patricia C, Chang, Judy C, Moses, Emily S, Dao, Tu, Chen, Yidong, Hung, Jaclyn Y
Format: Article
Language:English
Subjects:
Aberration
Agar
Aquaporins
Bioinformatics
Biology and Life Sciences
Brain Neoplasms - enzymology
Brain Neoplasms - pathology
Cancer
Cancer cells
Cancer therapies
Cell adhesion
Cell cycle
Cell growth
Cell Proliferation
Cell self-renewal
Child
Children
Differentiation (biology)
Enrichment
Enzymes
Female
Genes
Glioblastoma - enzymology
Glioblastoma - pathology
Glioma
Gliomas
Humans
Male
Medical prognosis
Medical research
Medicine and Health Sciences
Metastasis
Neoplasm Invasiveness
Neoplastic Stem Cells - pathology
Nervous system
Pathways
Pediatrics
Peptides
Proteins
Quality
Regulators
Research and Analysis Methods
Science
Signal transduction
Transcriptome
Tumors
Ubiquitin
Ubiquitin Thiolesterase - genetics
Ubiquitin Thiolesterase - metabolism
Viruses
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Summary:Pediatric high-grade gliomas represent 8-12% of all primary tumors of the nervous system in children. Five-year survival for these pediatric aggressive tumors is poor (15-35%) indicating the need to develop better treatments for pediatric high-grade gliomas. In this work we used SF188 and SJ-GBM2 cell lines to study the function of the ubiquitin carboxyl-terminal esterase L1 (UCHL1), a deubiquitinase de-regulated in several cancers, in pediatric high-grade gliomas. UCHL1 depletion in SF188 and SJ-GBM2 glioma cells was associated with decreased cell proliferation and invasion, along with a reduced ability to grow in soft agar and to form spheres (i.e. self-renewal measure). A 70% reduction in Wnt signaling was also observed in the SF188 and SJ-GBM2 UCHL1 knockdowns (KDs) using a TCF-dependent TOPflash reporter assay. Transcriptome comparisons of UCHL1 KDs versus vector control identified a list of 306 differentially expressed genes (at least 2-fold change; p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0176879