GON4L Drives Cancer Growth through a YY1-Androgen Receptor-CD24 Axis.
Cancer Res
; 76(17): 5175-85, 2016 09 01.
Article
em En
| MEDLINE
| ID: mdl-27312530
ABSTRACT
In principle, the inhibition of candidate gain-of-function genes defined through genomic analyses of large patient cohorts offers an attractive therapeutic strategy. In this study, we focused on changes in expression of CD24, a well-validated clinical biomarker of poor prognosis and a driver of tumor growth and metastasis, as a benchmark to assess functional relevance. Through this approach, we identified GON4L as a regulator of CD24 from screening a pooled shRNA library of 176 candidate gain-of-function genes. GON4L depletion reduced CD24 expression in human bladder cancer cells and blocked cell proliferation in vitro and tumor xenograft growth in vivo Mechanistically, GON4L interacted with transcription factor YY1, promoting its association with the androgen receptor to drive CD24 expression and cell growth. In clinical bladder cancer specimens, expression of GON4L, YY1, and CD24 was elevated compared with normal bladder urothelium. This pathway is biologically relevant in other cancer types as well, where CD24 and the androgen receptor are clinically prognostic, given that silencing of GON4L and YY1 suppressed CD24 expression and growth of human lung, prostate, and breast cancer cells. Overall, our results define GON4L as a novel driver of cancer growth, offering new biomarker and therapeutic opportunities. Cancer Res; 76(17); 5175-85. ©2016 AACR.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Neoplasias da Bexiga Urinária
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Carcinoma de Células de Transição
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Receptores Androgênicos
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Fator de Transcrição YY1
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Antígeno CD24
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article