Abstract
Abstract The role of Notch signaling in prostate cancer remains inconclusive. We show that a higher Notch signature score is significantly correlated with higher disease grade, metastatic potential and higher probability of lethal outcome in two published human prostate cancer datasets. We employ genetic approaches to investigate the role of Notch signaling in initiation and progression of prostate cancer in a Pten null mouse model. Notch signaling is dispensable for disease initiation and progression in this model. Elevated Notch activity in the Pten null model promotes both epithelial proliferation and apoptosis, which collectively results in a reduction of primary tumor burdens. Despite reduced primary tumor burdens, Notch activation drives epithelial-mesenchymal-transition and promotes distal tumor metastases at full penetrance. Our study reveals distinct impacts of Notch signaling on cancer cell proliferation, survival and metastasis in the context of Pten loss, and highlights a multifaceted and pleiotropic role of Notch in regulating the different aspects of prostate cancer cell biology. Citation Format: Oh-Joon Kwon, Li Zhang, Wang Jianghua, Chad Creighton, Michael Ittmann, Li Xin. Notch signaling promotes tumor metastasis in the Pten null mouse model for prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference: Developmental Biology and Cancer; Nov 30-Dec 3, 2015; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(4_Suppl):Abstract nr A36.
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