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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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
Total Authors: 11
Document type: Journal article
Source: ONCOTARGET; v. 8, n. 12, p. 19192-19204, 2017.
Web of Science Citations: 2
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: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
Grantee:Mayana Zatz
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 11/05534-8 - Transcription factor Oct4 and tumorigenic property of medulloblastoma
Grantee:Patrícia Benites Gonçalves da Silva
Support type: Scholarships in Brazil - Master
FAPESP's process: 13/17566-7 - Pluripotency factor OCT4A and aggressiveness of human medulloblastoma
Grantee:Patrícia Benites Gonçalves da Silva
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 13/02983-1 - Expression of hsa-miR-367 and aggressiveness of human medulloblastoma
Grantee:Carolini Kaid Dávila
Support type: Scholarships in Brazil - Master
FAPESP's process: 11/10001-9 - Contribution of mesenchymal stem cells to tumor development
Grantee:Carolina de Oliveira Rodini
Support type: 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 type: Regular Research Grants
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 type: Scholarships in Brazil - Post-Doctorate