RRC ID 65847
Author Chikaraishi K, Takenobu H, Sugino RP, Mukae K, Akter J, Haruta M, Kurosumi M, Endo TA, Koseki H, Shimojo N, Ohira M, Kamijo T.
Title CFC1 is a cancer stemness-regulating factor in neuroblastoma.
Journal Oncotarget
Abstract BACKGROUND:Despite the use of aggressive therapy, survival rates among high-risk neuroblastoma (NB) patients remain poor. Cancer stem cells (CSCs) are considered to be critically involved in the recurrence and metastasis of NB and are isolated as NB spheres.
METHODS:The gene expression profiling of adherent (control) and sphere-forming primary NB cells was conducted using a gene expression microarray. CFC1, which functions in the development of embryos and decides the left-right axis, was strongly expressed in sphere-forming cells only and was related to the unfavorable prognosis of NB patients. The knockdown and overexpression of CFC1 were performed using a lentiviral system in NB cell lines. Sphere formation, cell proliferation, colony formation in soft agar, and xenograft tumor formation were analyzed.
RESULTS:The overexpression of CFC1 increased sphere formation, cell growth, and colony formation. These phenotypes, particularly sphere formation, and xenograft tumor formation were significantly suppressed by the knockdown of CFC1. CFC1 inhibited Activin A-induced NB cell differentiation and Smad2 phosphorylation in NB cell lines, indicating its involvement in tumorigenesis related to EGF-CFC co-receptor family molecule pathways. Collectively, these results indicate that CFC1 is a candidate molecule for the development of CSC-targeted therapy for NB.
Volume 8(28)
Pages 45046-45059
Published 2017-7-11
DOI 10.18632/oncotarget.18464
PII 18464
PMID 28620148
PMC PMC5542166
MeSH Animals Cell Differentiation / physiology Cell Line, Tumor Cell Proliferation / physiology Female Gene Expression Profiling Heterografts Humans Intercellular Signaling Peptides and Proteins / genetics Intercellular Signaling Peptides and Proteins / metabolism* Mice Mice, Inbred BALB C Mice, Nude Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology Neuroblastoma / genetics Neuroblastoma / metabolism* Neuroblastoma / pathology Prognosis Transfection
IF 5.168
Human and Animal Cells IMR-32(RCB1895)