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

• Published in: Oncotarget Vol. 7; no. 8; pp. 9513 - 9524
• Main Authors: Xiao, Qianqian, Qian, Zunlei, Zhang, Weiqing, Liu, Jin, Hu, Enze, Zhang, Jinsan, Li, Mingying, Wang, Junhao, Kong, Fei, Li, Yunguang, Wang, Rui, Tan, Xiaohua, He, Dacheng, Xiao, Xueyuan
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 23.02.2016
• Subjects: A549 Cells; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Antibodies, Monoclonal - pharmacology; Apoptosis - genetics; Calcium-Binding Proteins - genetics; Cell Line, Tumor; Female; Humans; Lung Neoplasms - genetics; Mice; Mice, Inbred BALB C; Mice, Nude; Phosphoproteins - genetics; Phosphoproteins - metabolism; Protein Isoforms - genetics; Receptors, TNF-Related Apoptosis-Inducing Ligand - agonists; Receptors, TNF-Related Apoptosis-Inducing Ligand - biosynthesis; Receptors, TNF-Related Apoptosis-Inducing Ligand - metabolism; Research Paper; RNA Interference; RNA, Small Interfering - genetics; TNF-Related Apoptosis-Inducing Ligand - metabolism; Transcription Factors; Tumor Protein p73 - genetics; Tumor Protein p73 - metabolism; YAP; TRAIL; lung cancer cells; CABYR-a/b; DR5
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.7069

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.