title: Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells.
abstract: Glutaminolysis is important for metabolism and biosynthesis of cancer cells, and GLS is essential in the process. Selenite is widely regarded as a chemopreventive agent against cancer risk. Emerging evidence suggests that it also has chemotherapeutic potential in various cancer types, but the mechanism remains elusive. We demonstrate for the first time that supranutritional dose of selenite suppresses glutaminolysis by promoting GLS1 protein degradation and apoptosis. Mechanistically, selenite promotes association of APC/C-CDH1 with GLS1 and leads to GLS1 degradation by ubiquitination, this process is related to induction of PTEN expression. In addition, GLS1 expression is increased in human colorectal cancer tissues compared with normal mucosae. Our data provide a novel mechanistic explanation for the anti-cancer effect of selenite from a perspective of cell metabolism. Moreover, our results indicate that glutaminolysis especially GLS1 could be an attractive therapeutic target in colorectal cancer.
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University of Medicine, Wuhan, China.|The Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, China.|National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.|Department of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Junzhang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Zhongnan Hospital of Wuhan University of Medicine, Wuhan, China.|The Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases, Wuhan, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.|Tumor Laboratory, Department of Radiation Oncology, The Affiliated Lianyungang Hospital of Xuzhou Medical University, Lianyungang, China.
authors.forename: Kaiyuan
authors.initials: K
authors.lastname: Hui
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Union Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: QiuYue
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Ci
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Caimin
authors.initials: C
authors.lastname: Xu
authors.affiliation: Union Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.affiliation: Union Hospital, TongJi Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D015703:Antigens, CD; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D005972:Glutaminase / Q000378:metabolism; D005973:Glutamine / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D060888:Real-Time Polymerase Chain Reaction; D020887:Selenious Acid / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D015703:Antigens, CD; D000970:Antineoplastic Agents; C513384:CDH1 protein, human; D015820:Cadherins; D005973:Glutamine; C579480:GLS protein, human; D005972:Glutaminase; D020887:Selenious Acid
keywords: colorectal cancer; glutamnase; selenite