Role of DAB2IP in modulating epithelial-to-mesenchymal transition and prostate cancer metastasis

Daxing Xie, Crystal Gore, Jun Liu, Rey Chen Pong, Ralph Mason, Guiyang Hao, Michael Long, Wareef Kabbani, Luyang Yu, Haifeng Zhang, Hong Chen, Xiankai Sun, David A. Boothman, Wang Min, Jer Tsong Hsieh

Research output: Contribution to journalArticlepeer-review

171 Scopus citations

Abstract

A single nucleotide polymorphism in the DAB2IP gene is associated with risk of aggressive prostate cancer (PCa), and loss of DAB2IP expression is frequently detected in metastatic PCa. However, the functional role of DAB2IP in PCa remains unknown. Here, we show that the loss of DAB2IP expression initiates epithelial-to-mesenchymal transition (EMT), which is visualized by repression of E-cadherin and up-regulation of vimentin in both human normal prostate epithelial and prostate carcinoma cells as well as in clinical prostate-cancer specimens. Conversely, restoring DAB2IP in metastatic PCa cells reversed EMT. In DAB2IP knockout mice, prostate epithelial cells exhibited elevated mesenchymal markers, which is characteristic of EMT. Using a human prostate xenograft-mousemodel,weobserved that knocking down endogenous DAB2IP in human carcinoma cells led to the development of multiple lymph node and distant organ metastases. Moreover, we showed that DAB2IP functions as a scaffold protein in regulating EMT by modulating nuclear β-catenin/T-cell factor activity. These results show the mechanism of DAB2IP in EMT and suggest that assessment of DAB2IPmay provide a prognostic biomarker and potential therapeutic target for PCa metastasis.

Original languageEnglish (US)
Pages (from-to)2485-2490
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number6
DOIs
StatePublished - Feb 9 2010

ASJC Scopus subject areas

  • General

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