Oncotarget

Research Papers:

A switch from CD44+ cell to EMT cell drives the metastasis of prostate cancer

Zhiqun Shang, Qiliang Cai, Minghao Zhang, Shimiao Zhu, Yuan Ma, Libin Sun, Ning Jiang, Jing Tian, Xiaodan Niu, Jiatong Chen, Yinghao Sun and Yuanjie Niu _

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Oncotarget. 2015; 6:1202-1216. https://doi.org/10.18632/oncotarget.2841

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Abstract

Zhiqun Shang1, Qiliang Cai1, Minghao Zhang1, Shimiao Zhu1, Yuan Ma1, Libin Sun1, Ning Jiang1, Jing Tian1, Xiaodan Niu2, Jiatong Chen3, Yinghao Sun4 and Yuanjie Niu1

1 Sex Hormone Research Center, Tianjin Institute of Urology, the Second Hospital of Tianjin Medical University, Tianjin, China

2 University of Rochester, Rochester, New York, USA

3 Department of Biochemistry and Molecular Biology, College of Life Sciences, Nankai university, Tianjin, China

4 Department of Urology, Changhai Hospital of the Second Military Medical University, Shanghai, China

Correspondence:

Yuanjie Niu, email:

Keywords: androgen deprivation therapy, epithelial-mesenchymal transition, TGFβ1, cancer stem cell, CD44, prostate cancer

Received: August 23, 2014 Accepted: November 24, 2014 Published: November 25, 2014

Abstract

Epithelial–mesenchymal transition (EMT) has been linked to cancer stem-like (CD44+) cell in the prostate cancer (PCa) metastasis. However, the molecular mechanism remains elusive. Here, we found EMT contributed to metastasis in PCa patients failed in androgen deprivation therapy (ADT). Castration TRAMP model also proved PCa treated with ADT promoted EMT with increased CD44+ stem-like cells. Switched CD44+ cell to EMT cell is a key step for luminal PCa cell metastasis. Our results also suggested ADT might go through promoting TGFβ1-CD44 signaling to enhance swift to EMT. Targeting CD44 with salinomycin and siRNA could inhibit cell transition and decrease PCa invasion. Together, cancer stem-like (CD44+) cells could be the initiator cells of EMT modulated by TGFβ1-CD44 signaling. Combined therapy of ADT with anti-CD44 may become a new potential therapeutic approach to battle later stage PCa.


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