High OCT4A levels drive tumorigenicity and metastatic potential of medulloblastoma cells

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Goncalves da Silva, Patricia Benites ; Teixeira dos Santos, Marcia Cristina ; Rodini, Carolina Oliveira ; Kaid, Carolini ; Leite Pereira, Marcia Cristina ; Furukawa, Gabriela ; Gimenes da Cruz, Daniel Sanzio ; Goldfeder, Mauricio Barbugiani ; Reily Rocha, Clarissa Ribeiro ; Rosenberg, Carla ; Okamoto, Oswaldo Keith

• Document type: Journal article
• Source: ONCOTARGET; v. 8, n. 12, p. 19192-19204, 2017.
• Web of Science Citations: 3

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. (AU)

• FAPESP's process: 11/51588-2 - Functional characterization of the LIN28 protein in tumorigenesis of the central nervous system
• Grantee: Márcia Cristina Teixeira dos Santos
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/05534-8 - Transcription factor Oct4 and tumorigenic property of medulloblastoma
• Grantee: Patrícia Benites Gonçalves da Silva
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 11/10001-9 - Contribution of mesenchymal stem cells to tumor development
• Grantee: Carolina de Oliveira Rodini
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/52686-5 - E2F2 transcription factor and expression of proto-oncogenes in human embryonic stem cells
• Grantee: Oswaldo Keith Okamoto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/02983-1 - Expression of hsa-miR-367 and aggressiveness of human medulloblastoma
• Grantee: Carolini Kaid Dávila
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 13/17566-7 - Pluripotency factor OCT4A and aggressiveness of human medulloblastoma
• Grantee: Patrícia Benites Gonçalves da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)