Oncotarget

Research Papers:

Fas-associated protein with death domain (FADD) regulates autophagy through promoting the expression of Ras homolog enriched in brain (Rheb) in human breast adenocarcinoma cells

Liangqiang He _, Yongzhe Ren, Qianqian Zheng, Lu Wang, Yueyang Lai, Shengwen Guan, Xiaoxin Zhang, Rong Zhang, Jie Wang, Dianhua Chen, Yunwen Yang, Hongqin Zhuang, Wei Cheng, Jing Zhang and Zi-chun Hua

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Oncotarget. 2016; 7:24572-24584. https://doi.org/10.18632/oncotarget.8249

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Abstract

Liangqiang He1, Yongzhe Ren1, Qianqian Zheng1, Lu Wang1, Yueyang Lai1, Shengwen Guan2, Xiaoxin Zhang1, Rong Zhang1, Jie Wang1, Dianhua Chen1, Yunwen Yang1, Hongqin Zhuang1, Wei Cheng1, Jing Zhang1, Zi-chun Hua1,2

1The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, Jiangsu, China

2Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc., Changzhou, 213164, Jiangsu, China

Correspondence to:

Zi-chun Hua, e-mail: zchua@nju.edu.cn

Jing Zhang, e-mail: jzhang08@nju.edu.cn

Wei Cheng, e-mail: chengwe@outlook.com

Keywords: FADD, Rheb, autophagy, tumorigenesis, breast cancer

Received: August 06, 2015    Accepted: March 01, 2016    Published: March 22, 2016

ABSTRACT

FADD (Fas-associated protein with death domain) is a classical adaptor protein in apoptosis. Increasing evidences have shown that FADD is also implicated in cell cycle progression, proliferation and tumorigenesis. The role of FADD in cancer remains largely unexplored. In this study, In Silico Analysis using Oncomine and Kaplan Meier plotter revealed that FADD is significantly up-regulated in breast cancer tissues and closely associated with a poor prognosis in patients with breast cancer. To better understanding the FADD functions in breast cancer, we performed proteomics analysis by LC-MS/MS detection and found that Rheb–mTORC1 pathway was dysregulated in MCF-7 cells when FADD knockdown. The mTORC1 pathway is a key regulator in many processes, including cell growth, metabolism and autophagy. Here, FADD interference down-regulated Rheb expression and repressed mTORC1 activity in breast cancer cell lines. The autophagy was induced by FADD deficiency in MCF7 or MDA-231 cells but rescued by recovering Rheb expression. Similarly, growth defect in FADD-knockdown cells was also restored by Rheb overexpression. These findings implied a novel role of FADD in tumor progression via Rheb–mTORC1 pathway in breast cancer.


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