title: Promyelocytic leukemia protein enhances apoptosis of gastric cancer cells through Yes-associated protein.
abstract: It has been shown that Yes-associated protein (YAP) acts as a transcriptional co-activator to regulate p73-dependent apoptosis in response to DNA damage in some cell types, and promyelocytic leukemia (PML) protein is involved in the regulation loop through stabilization of YAP through sumoylation. Although YAP has been shown to be significantly upregulated in gastric cancer, whether the YAP/PML/p73 regulation loop also functions in gastric cancer is unknown. Here, we show significantly higher levels of YAP and significantly lower levels of PML in the gastric cancer specimen. Overexpression of YAP in gastric cancer cells significantly increased cell growth, but did not affect apoptosis. However, overexpression of PML in gastric cancer cells significantly increased cell apoptosis, resulting in decreases in cell growth, which seemed to require the presence of YAP. The effect of PML on apoptosis appeared to be conducted through p73-mediated modulation of apoptosis-associated genes, Bcl-2, Bak, and caspase9. Thus, our study suggests the presence of a YAP/PML/p73 regulatory loop in gastric cancer, and highlights PML as a promising tumor suppressor in gastric cancer through YAP-coordinated cancer cell apoptosis.
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China. xuzhipeng_1978@163.com.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Shao
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China.
authors.forename: Wangqian
authors.initials: W
authors.lastname: Ma
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, 310009, China.
authors.forename: Dingting
authors.initials: D
authors.lastname: Xu
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D051575:Proto-Oncogene Proteins c-yes / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D012333:RNA, Messenger; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human; D051575:Proto-Oncogene Proteins c-yes; C489834:YES1 protein, human
keywords: Apoptosis; Gastric cancer; Promyelocytic leukemia (PML); Yes-associated protein (YAP)