Susceptibility-Associated Genetic Variation in NEDD9 Contributes to Prostate Cancer Initiation and Progression
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Feb 25, 2021
- Source ID
- 10.1158/0008-5472.can-20-3042
Entities
People
- Bridget M. Healy
- Changmeng Cai
- Dong Han
- Jill Macoska
- Jocelyn S. Steinfeld
- Jude N. Owiredu
- Kellee R Siegfried
- Kourosh Zarringhalam
- Maryam Labaf
- Mingyu Liu
- Muqing Li
- Shuai Gao
- Susan Patalano
- Timothy R Rebbeck
- Xin Yuan
Organizations
- Harvard Medical School
- Harvard University
- National Institutes of Health
- University of Massachusetts Boston