Oncotarget

Research Papers:

Depletion of CABYR-a/b sensitizes lung cancer cells to TRAIL-induced apoptosis through YAP/p73-mediated DR5 upregulation

Qianqian Xiao, Zunlei Qian, Weiqing Zhang, Jin Liu, Enze Hu, Jinsan Zhang, Mingying Li, Junhao Wang, Fei Kong, Yunguang Li, Rui Wang, Xiaohua Tan, Dacheng He and Xueyuan Xiao _

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Oncotarget. 2016; 7:9513-9524. https://doi.org/10.18632/oncotarget.7069

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Abstract

Qianqian Xiao1,*, Zunlei Qian1,2,*, Weiqing Zhang1, Jin Liu1, Enze Hu1, Jinsan Zhang3, Mingying Li1,4, Junhao Wang1, Fei Kong1, Yunguang Li1, Rui Wang1, Xiaohua Tan3, Dacheng He1, Xueyuan Xiao1

1Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China

2College of Forensic Sciences, People’s Public Security University of China, Beijing, China

3School of Pharmaceutical Sciences and Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, China

4Center of Reproduction and Genetics, First People’s Hospital of Yunnan Province, Kunming, China

*These authors contributed equally to this work

Correspondence to:

Xueyuan Xiao, e-mail: [email protected], [email protected]

Keywords: CABYR-a/b, lung cancer cells, DR5, TRAIL, YAP

Received: August 18, 2015     Accepted: January 13, 2016     Published: January 29, 2016

ABSTRACT

Our previous study revealed that knockdown of CABYR-a/b increases the chemosensitivity of lung cancer cells through inactivation of Akt. Here, we demonstrated that depletion of CABYR-a/b significantly increased DR5 expression and sensitized lung cancer cells to TRAIL-induced apoptosis in vitro and/or in vivo. Importantly, treatment with AD5-10, a DR5-specific agonistic monoclonal antibody, was able to mimic TRAIL-induced apoptosis in CABYR-a/b-silenced cells. Strikingly, we identified that depletion of CABYR-a/b not only increased the expressions of p73 and DR5 but also decreased the phosphorylation of YAP S127. Loss- or gain-of-function studies of YAP and p73 revealed that double deletions of YAP and p73 effectively decreased the expression of DR5 and abolished TRAIL-induced apoptosis in CABYR-a/b knockdown cells. Conversely, the co-overexpression of YAP and p73 promoted the expression of DR5 and sensitized cells to TRAIL-induced apoptosis. Taken together, our results demonstrate that depletion of CABYR-a/b sensitizes lung cancer cells to TRAIL-induced apoptosis through YAP/p73-mediated DR5 upregulation.


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