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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Identification of a Cyclin D1 Network in Prostate Cancer That Antagonizes Epithelial-Mesenchymal Restraint
Cancer research (Chicago, Ill.), v 74(2), pp 508-519
15 Jan 2014
PMID: 24282282
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Improved clinical management of prostate cancer has been impeded by an inadequate understanding of molecular genetic elements governing tumor progression. Gene signatures have provided improved prognostic indicators of human prostate cancer. The TGF-beta/BMP-SMAD4 signaling pathway, which induces epithelial-mesenchymal transition (EMT), is known to constrain prostate cancer progression induced by Pten deletion. Herein, cyclin D1 inactivation reduced cellular proliferation in the murine prostate in vivo and in isogenic oncogene-transformed prostate cancer cell lines. The in vivo cyclin D1-mediated molecular signature predicted poor outcome of recurrence-free survival for patients with prostate cancer (K-means HR, 3.75, P = 0.02) and demonstrated that endogenous cyclin D1 restrains TGF-beta, Snail, Twist, and Goosecoid signaling. Endogenous cyclin D1 enhanced Wnt and ES cell gene expression and expanded a prostate stem cell population. In chromatin immunoprecipitation sequencing, cyclin D1 occupied genes governing stem cell expansion and induced their transcription. The coordination of EMT restraining and stem cell expanding gene expression by cyclin D1 in the prostate may contribute to its strong prognostic value for poor outcome in biochemical-free recurrence in human prostate cancer.
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Details
- Title
- Identification of a Cyclin D1 Network in Prostate Cancer That Antagonizes Epithelial-Mesenchymal Restraint
- Creators
- Xiaoming Ju - Kimmel Cancer CenterMathew C. Casimiro - Kimmel Cancer CenterMichael Gormley - Thomas Jefferson UniversityHui Meng - Kimmel Cancer CenterXuanmao Jiao - Kimmel Cancer CenterSanjay Katiyar - Thomas Jefferson UniversityMarco Crosariol - Thomas Jefferson UniversityKe Chen - Thomas Jefferson UniversityMin Wang - Thomas Jefferson UniversityAndrew A. Quong - Thomas Jefferson UniversityMichael P. Lisanti - Breast Cancer Research FoundationAdam Ertel - Thomas Jefferson UniversityRichard G. Pestell - Thomas Jefferson University
- Publication Details
- Cancer research (Chicago, Ill.), v 74(2), pp 508-519
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 12
- Grant note
- Pennsylvania Department of Health 1P30CA56036-08 / Kimmel Cancer Center Dr. Ralph and Marian C. Falk Medical Research Trust R01CA075503 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000330034200011
- Scopus ID
- 2-s2.0-84892933645
- Other Identifier
- 991019176793804721
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- Web of Science research areas
- Oncology