Oncotarget

Research Papers:

Notch3 overexpression enhances progression and chemoresistance of urothelial carcinoma

Heng Zhang, Limei Liu, Chungang Liu, Jinhong Pan, Gensheng Lu, Zhansong Zhou, Zhiwen Chen and Cheng Qian _

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Oncotarget. 2017; 8:34362-34373. https://doi.org/10.18632/oncotarget.16156

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Abstract

Heng Zhang1,2, Limei Liu1, Chungang Liu1, Jinhong Pan2, Gensheng Lu2, Zhansong Zhou2, Zhiwen Chen2, Cheng Qian1

1Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China

2Department of Urology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China

Correspondence to:

Cheng Qian, email: cqian3184@163.com

Zhiwen Chen, email: zhiwen@tmmu.edu.cn

Keywords: Notch3, urothelial cancer, cisplatin, histone deacetylase, chemoresistance

Received: March 14, 2016     Accepted: December 12, 2016     Published: March 13, 2017

ABSTRACT

Abnormal activation of Notch signaling is involved in the etiology of various diseases, including cancer, but the association between Notch3 expression in urothelial cancer and clinical outcome remains unclear, and the molecular mechanisms underlying Notch3 signaling activation are not well defined. In this study we examined 59 urothelial cancer patients and found that Notch3 was more highly expressed in human urothelial cancer tissues than in non-tumorous bladder tissue samples, with Notch3 overexpression being associated with poor clinical outcome. Notch3 knockdown resulted in decreased proliferation of urothelial cancer cells in vitro and decreased xenograft tumor growth in vivo. In addition, Notch3 knockdown rendered urothelial cancer cells more sensitive to cisplatin. Furthermore, suberoylanilide hydroxamic acid (SAHA, a histone deacetylase [HDAC] inhibitor) induced acetylation of NOTCH3, downregulated Notch 3, prevented urothelial cancer cell proliferation, and induced cell cycle arrest. Taken together, these data suggested that Notch 3 overexpression promotes growth and chemoresistance in urothelial cancer.


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