CFC1 is a cancer stemness-regulating factor in neuroblastoma

• Published in: Oncotarget 2017-07, Vol.8 (28), p.45046-45059
• Main Authors: Chikaraishi, Koji, Takenobu, Hisanori, Sugino, Ryuichi P, Mukae, Kyosuke, Akter, Jesmin, Haruta, Masayuki, Kurosumi, Masafumi, Endo, Takaho A, Koseki, Haruhiko, Shimojo, Naoki, Ohira, Miki, Kamijo, Takehiko
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 1949-2553
• DOI: 10.18632/oncotarget.18464

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. 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. 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.