Genetic Ablation of Metadherin Inhibits Autochthonous Prostate Cancer Progression and Metastasis

Overview

Journal Cancer Res

Specialty Oncology

Date 2014 Jul 31

PMID 25074613

Citations 26

Authors

Liling Wan

Guohong Hu

Yong Wei

Min Yuan

Roderick T Bronson

Qifeng Yang

Javed Siddiqui

Kenneth J Pienta

Yibin Kang

Affiliations

Soon will be listed here.

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.

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