Susceptibility-Associated Genetic Variation in NEDD9 Contributes to Prostate Cancer Initiation and Progression
| Autor: | Dong Han, Maryam Labaf, Changmeng Cai, Xin Yuan, Muqing Li, Kourosh Zarringhalam, Susan Patalano, Timothy R. Rebbeck, Shuai Gao, Mingyu Liu, Jill A. Macoska, Jocelyn S. Steinfeld, Kellee R. Siegfried, Bridget M. Healy, Jude N. Owiredu |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty education.field_of_study business.industry Chromatin binding Population Cancer medicine.disease NEDD9 Metastasis 03 medical and health sciences Prostate cancer 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Internal medicine Genetic variation medicine SNP business education |
| Zdroj: | Cancer Research. 81:3766-3776 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-20-3042 |
| Popis: | Although American men of European ancestry represent the largest population of patients with prostate cancer, men of African ancestry are disproportionately affected by prostate cancer, with higher prevalence and worse outcomes. These racial disparities in prostate cancer are due to multiple factors, but variations in genomic susceptibility such as SNP may play an important role in determining cancer aggressiveness and treatment outcome. Using public databases, we have identified a prostate cancer susceptibility SNP at an intronic enhancer of the neural precursor expressed, developmentally downregulated 9 (NEDD9) gene, which is strongly associated with increased risk of patients with African ancestry. This genetic variation increased expression of NEDD9 by modulating the chromatin binding of certain transcription factors, including ERG and NANOG. Moreover, NEDD9 displayed oncogenic activity in prostate cancer cells, promoting prostate cancer tumor growth and metastasis in vitro and in vivo. Together, our study provides novel insights into the genetic mechanisms driving prostate cancer racial disparities. Significance: A prostate cancer susceptibility genetic variation in NEDD9, which is strongly associated with the increased risk of patients with African ancestry, increases NEDD9 expression and promotes initiation and progression of prostate cancer. See related commentary by Mavura and Huang, p. 3764 |
| Databáze: | OpenAIRE |
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