Endostatin: A novel inhibitor of androgen receptor function in prostate cancer
Abstract
Despite the development of second-generation androgen receptor (AR)-targeted therapies for castration-resistant prostate cancer (CRPC), the effects are only modest, compelling the need for novel therapy combinations that can maximize the antitumor effects of new-generation chemotherapies with minimal acquired resistance, attributed to AR modifications. The present study identified that endostatin (ES), known for its antiangiogenic properties on tumor vasculature, exerts a profound antiproliferative effect on AR-positive human PCa cells. By a systematic approach involving a combination of in situ, cell-free, yeast-two hybrid, structural modeling, and mutagenesis studies, we determined that intracellular trafficking of ES in AR-positive PCa cells leads to a direct interaction with AR in the cytosol, affecting the transcriptional activation of AR target genes.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 20, 2015
- Source ID
- 10.1073/pnas.1417660112
Entities
People
- Anandi Sawant
- Diptiman Chanda
- Ha-ram Cha
- Igor N. Chesnokov
- Joo Hyoung Lee
- Matthew R. Larson
- Selvarangan Ponnazhagan
- Tatyana Isayeva
Organizations
- National Institutes of Health
- United States Army Medical Research and Development Command
- University of Alabama
- University of Michigan