title: High OCT4A levels drive tumorigenicity and metastatic potential of medulloblastoma cells.
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.
authors.affiliation: Centro de Pesquisa sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Patrícia Benites Gonçalves
authors.initials: PBG
authors.lastname: da Silva
authors.affiliation: Centro de Pesquisa sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Márcia Cristina
authors.initials: MC
authors.lastname: Teixeira Dos Santos
authors.affiliation: Centro de Pesquisa sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Carolina Oliveira
authors.initials: CO
authors.lastname: Rodini
authors.affiliation: Centro de Pesquisa sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Carolini
authors.initials: C
authors.lastname: Kaid
authors.affiliation: Centro de Pesquisa sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Márcia Cristina Leite
authors.initials: MCL
authors.lastname: Pereira
authors.affiliation: Centro de Pesquisa sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Furukawa
authors.affiliation: Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Daniel Sanzio Gimenes
authors.initials: DSG
authors.lastname: da Cruz
authors.affiliation: Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo, SP, Brazil.
authors.forename: Mauricio Barbugiani
authors.initials: MB
authors.lastname: Goldfeder
authors.affiliation: Departmento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Clarissa Ribeiro Reily
authors.initials: CRR
authors.lastname: Rocha
authors.affiliation: Centro de Pesquisa sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Rosenberg
authors.affiliation: Centro de Pesquisa sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil.
authors.forename: Oswaldo Keith
authors.initials: OK
authors.lastname: Okamoto
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D002465:Cell Movement; D049109:Cell Proliferation; D002528:Cerebellar Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human
keywords: LIN28A; OCT4A; POU5F1; aggressiveness; medulloblastoma