Depletion of CABYR-a/b sensitizes lung cancer cells to TRAIL-induced apoptosis through YAP/p73-mediated DR5 upregulation
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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
Keywords: CABYR-a/b, lung cancer cells, DR5, TRAIL, YAP
Received: August 18, 2015 Accepted: January 13, 2016 Published: January 29, 2016
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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