FOXA2 promotes prostate cancer growth in the bone

FOXA2 促进骨骼中前列腺癌的生长

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作者: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

Abstract

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.

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