title: Depletion of CABYR-a/b sensitizes lung cancer cells to TRAIL-induced apoptosis through YAP/p73-mediated DR5 upregulation.
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.
authors: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors: Qianqian
authors: Q
authors: Xiao
authors: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.|College of Forensic Sciences, People's Public Security University of China, Beijing, China.
authors: Zunlei
authors: Z
authors: Qian
authors: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors: Weiqing
authors: W
authors: Zhang
authors: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors: Jin
authors: J
authors: Liu
authors: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors: Enze
authors: E
authors: Hu
authors: School of Pharmaceutical Sciences and Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors: Jinsan
authors: J
authors: Zhang
authors: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.|Center of Reproduction and Genetics, First People's Hospital of Yunnan Province, Kunming, China.
authors: Mingying
authors: M
authors: Li
authors: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors: Junhao
authors: J
authors: Wang
authors: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors: Fei
authors: F
authors: Kong
authors: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors: Yunguang
authors: Y
authors: Li
authors: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors: Rui
authors: R
authors: Wang
authors: School of Pharmaceutical Sciences and Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors: Xiaohua
authors: X
authors: Tan
authors: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors: Dacheng
authors: D
authors: He
authors: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing, China.
authors: Xueyuan
authors: X
authors: Xiao
mesh_terms: D000072283:A549 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D014157:Transcription Factors; D000072160:Tumor Protein p73 / Q000235:genetics / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; C448922:CABYR protein, human; D002135:Calcium-Binding Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; C000606460:TP73 protein, human; D014157:Transcription Factors; D000072160:Tumor Protein p73; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human
keywords: CABYR-a/b; DR5; TRAIL; YAP; lung cancer cells