1. High OCT4A levels drive tumorigenicity and metastatic potential of medulloblastoma cells.
- Author
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da Silva PBG, Teixeira Dos Santos MC, Rodini CO, Kaid C, Pereira MCL, Furukawa G, da Cruz DSG, Goldfeder MB, Rocha CRR, Rosenberg C, and Okamoto OK
- Subjects
- Animals, Apoptosis, Biomarkers, Tumor genetics, Brain Neoplasms genetics, Brain Neoplasms metabolism, Cell Movement, Cell Proliferation, Cerebellar Neoplasms genetics, Cerebellar Neoplasms metabolism, Female, Humans, Medulloblastoma genetics, Medulloblastoma metabolism, Mice, Mice, Inbred BALB C, Mice, Nude, Octamer Transcription Factor-3 genetics, Prognosis, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Biomarkers, Tumor metabolism, Brain Neoplasms secondary, Cerebellar Neoplasms pathology, Medulloblastoma pathology, Octamer Transcription Factor-3 metabolism
- Abstract
Medulloblastoma is a highly aggressive pediatric brain tumor, in which sporadic expression of the pluripotency factor OCT4 has been recently correlated with poor patient survival. However the contribution of specific OCT4 isoforms to tumor aggressiveness is still poorly understood. Here, we report that medulloblastoma cells stably overexpressing the OCT4A isoform displayed enhanced clonogenic, tumorsphere generation, and invasion capabilities. Moreover, in an orthotopic metastatic model of medulloblastoma, OCT4A overexpressing cells generated more developed, aggressive and infiltrative tumors, with tumor-bearing mice attaining advanced metastatic disease and shorter survival rates. Pro-oncogenic OCT4A effects were expression-level dependent and accompanied by distinct chromosomal aberrations. OCT4A overexpression in medulloblastoma cells also induced a marked differential expression of non-coding RNAs, including poorly characterized long non-coding RNAs and small nucleolar RNAs. Altogether, our findings support the relevance of pluripotency-related factors in the aggravation of medulloblastoma traits classically associated with poor clinical outcome, and underscore the prognostic and therapeutic value of OCT4A in this challenging type of pediatric brain cancer.
- Published
- 2017
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