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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.)

Embryonic Stem Cell-Related Protein L1TD1 Is Required for Cell Viability, Neurosphere Formation, and Chemoresistance in Medulloblastoma

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Author(s):
Teixeira Santos, Marcia Cristina [1] ; Goncalves Silva, Patricia Benites [1] ; Rodini, Carolina Oliveira [1] ; Furukawa, Gabriela [1] ; Marco Antonio, David Santos [1] ; Zanotto-Filho, Alfeu [2] ; Moreira, Jose C. F. [2] ; Okamoto, Oswaldo Keith [1]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Biosci Inst, Dept Genet & Evolutionary Biol, Human Genome & Stem Cell Res Ctr, BR-05508090 Sao Paulo - Brazil
[2] Univ Fed Rio Grande do Sul, Oxidat Stress Res Ctr, Dept Biochem, Porto Alegre, RS - Brazil
Total Affiliations: 2
Document type: Journal article
Source: STEM CELLS AND DEVELOPMENT; v. 24, n. 22, p. 2700-2708, NOV 15 2015.
Web of Science Citations: 5
Abstract

Misexpression of stem cell-related genes may occur in some cancer cells, influencing patient's prognosis. This is the case of medulloblastoma, a common and clinically challenging malignant tumor of the central nervous system, where expression of the pluripotency factor, OCT4, is correlated with poor survival. A downstream target of OCT4, L1TD1 (LINE-1 type transposase domain-containing protein 1 family member), encodes a novel embryonic stem cell (ESC)-related protein involved in pluripotency and self-renewal of ESCs. L1TD1 is still poorly characterized and its expression pattern and function in cancer cells are virtually unknown. Although normally restricted to non-neoplastic undifferentiated cells and germ cells, we found that high L1TD1 expression also occurs in medulloblastoma cells, reaching levels similar to those found in ESCs, and is correlated with poor prognosis. Conversely to what is reported during normal cell differentiation, when differentiated cells remain healthy, despite L1TD1 downregulation, depletion of L1TD1 protein levels by targeted gene silencing significantly reduced medulloblastoma cell viability, inhibiting cell proliferation and inducing apoptosis. More strikingly, L1TD1 depletion downregulated expression of the neural stem cell markers, CD133 and Nestin, inhibited neurosphere generation capability, and sensitized medulloblastoma cells to temozolomide and cisplatin, two chemotherapeutic agents of clinical relevance in medulloblastoma treatment. Our findings provide insights about the contribution of pluripotency-related genes to a more aggressive tumor phenotype through their involvement in the acquisition of stem-like properties by cancer cells and point out L1TD1 as a potential therapeutic target in malignant brain tumors. (AU)

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: 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: 13/08028-1 - 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: 11/51588-2 - 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
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