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Data Supplement from Genetic Ablation of Metadherin Inhibits Autochthonous Prostate Cancer Progression and Metastasis

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posted on 2023-03-30, 22:40 authored by Liling Wan, Guohong Hu, Yong Wei, Min Yuan, Roderick T. Bronson, Qifeng Yang, Javed Siddiqui, Kenneth J. Pienta, Yibin Kang

Supplementary Methods, Figures 1-5, Table 1. Supplementary Materials and Methods. Supplemental Figure S1. Whole-organism knockout of Mtdh does not affect prostate gland development. Supplemental Figure S2. Mtdh ablation does not affect the expression of Probasin promoter-driven expression of SV40 antigens. Supplemental Figure S3. Loss of Mtdh inhibits the formation of diverse subtypes of prostate cancer in TRAMP mice. Supplemental Figure S4. Analyses of proliferation and apoptosis indices in prostate tissues from TRAMP/Mtdh+ and TRAMP/Mtdh- mice. Supplemental Figure S5. Silencing of Mtdh in TRAMP-C1 tumor cells impairs tumor formation in vivo. Supplemental Table 1: Clinical sample information for IHC and FISH analysis.

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ARTICLE ABSTRACT

Metadherin (MTDH) overexpression in diverse cancer types has been linked to poor clinical outcomes, but definitive genetic proof of its contributions to cancer remains incomplete. In particular, the degree to which MTDH may contribute to malignant progression in vivo is lacking. Here, we report that MTDH is amplified frequently in human prostate cancers where its expression levels are tightly correlated with prostate cancer progression and poor disease-free survival. Furthermore, we show that genetic ablation of MTDH in the transgenic adenomcarcinoma of mouse prostate (TRAMP) transgenic mouse model of prostate cancer blocks malignant progression without causing defects in the normal development of the prostate. Germline deletion of Mtdh in TRAMP mice prolonged tumor latency, reduced tumor burden, arrested progression of prostate cancer at well-differentiated stages, and inhibited systemic metastasis to distant organs, thereby decreasing cancer-related mortality ∼10-fold. Consistent with these findings, direct silencing of Mtdh in prostate cancer cells decreased proliferation in vitro and tumor growth in vivo, supporting an epithelial cell–intrinsic role of MTDH in prostate cancer. Together, our findings establish a pivotal role for MTDH in prostate cancer progression and metastasis and define MTDH as a therapeutic target in this setting. Cancer Res; 74(18); 5336–47. ©2014 AACR.