Bone metastasis frequently occurs in advanced-stage prostate cancer (PCa) patients. Understanding the mechanisms that promote PCa-mediated bone destruction is important for the identification of therapeutic targets against this lethal disease. We found that forkhead box A2 (FOXA2) is expressed in a subset of PCa bone metastasis specimens. To determine the functional role of FOXA2 in PCa metastasis, we knocked down the expression of FOXA2 in PCa PC3 cells, which can grow in bones and elicit an osteolytic reaction. The PC3/FOXA2-knockdown cells generated fewer bone lesions following intra-tibial injection compared to control cells. Further, we found that FOXA2 knockdown decreased the expression of PTHLH, which encodes PTHrP, a well-established factor that regulates bone remodeling. These results indicate that FOXA2 is involved in PCa bone metastasis.
American journal of translational research. 2020 Sep 15*** epublish ***
Zachary M Connelly, Renjie Jin, Jianghong Zhang, Shu Yang, Siyuan Cheng, Mingxia Shi, Justin Mm Cates, Runhua Shi, David J DeGraff, Peter S Nelson, Yunlong Liu, Colm Morrissey, Eva Corey, Xiuping Yu
Department of Biochemistry and Molecular Biology, LSU Health Shreveport, LA, USA., Department of Urological Surgery, Vanderbilt University Medical Center Nashville, TN, USA., Department of Pathology, University of South Alabama Mobile, AL, USA., Department of Pathology, Vanderbilt University Medical Center Nashville, TN, USA., Department of Medicine, LSU Health Shreveport, LA, USA., Department of Pathology, Penn State College of Medicine Hershey, PA, USA., Fred Hutchinson Cancer Research Center Seattle, WA, USA., Department of Biochemistry and Molecular Biology, Indiana University Indianapolis, IN, USA., Department of Urology, University of Washington Seattle, WA, USA.