Oncotarget

Research Papers:

FOXO3a promotes gastric cancer cell migration and invasion through the induction of cathepsin L

Shan Yu _, Yiyi Yu, Wen Zhang, Wei Yuan, Naiqing Zhao, Qian Li, Yuehong Cui, Yan Wang, Wei Li, Yihong Sun and Tianshu Liu

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Oncotarget. 2016; 7:34773-34784. https://doi.org/10.18632/oncotarget.8977

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Abstract

Shan Yu1,*, Yiyi Yu1,*, Wen Zhang1, Wei Yuan2, Naiqing Zhao3, Qian Li1, Yuehong Cui1, Yan Wang1, Wei Li1, Yihong Sun4, Tianshu Liu1

1Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

2Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

3Department of Biostatistics, Fudan University, Shanghai, People’s Republic of China

4Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China

*These authors have contributed equally to this work

Correspondence to:

Tianshu Liu, e-mail: liutianshu1969@126.com

Yihong Sun, e-mail: Sun.yihong@zs-hospital.sh.cn

Keywords: FOXO3a, cathepsin L, gastric cancer migration, invasion

Received: November 24, 2015     Accepted: April 11, 2016     Published: April 25, 2016

ABSTRACT

Forkhead box O3A (FOXO3a) is an important transcription factor involved in various human cancers. However, the role of FOXO3a in regulating the invasion and metastasis of gastric cancer cells has not been clarified. Here, we report that FOXO3a overexpression promoted migration and invasion of gastric cancer cells by upregulating cathepsin L. FOXO3a knockdown suppressed migration and invasion and also downregulated cathepsin L expression in gastric cancer cells. Silencing cathepsin L in these cells suppressed FOXO3a overexpression-induced cell migration and invasion. Mechanistic studies revealed that FOXO3a increased cathepsin L promoter activation, and cathepsin L overexpression repressed E-cadherin expression, causing gastric cancer cells to undergo epithelial-mesenchymal transition (EMT). Our data reveal a previously unexplored function of FOXO3a in gastric cancer invasion by regulating proteins involved in extracellular matrix (ECM) degradation and EMT. We suggest that FOXO3a may be of prognostic value and a potential therapeutic target in blocking tumor metastasis.


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