title: Nestin regulates proliferation and invasion of gastrointestinal stromal tumor cells by altering mitochondrial dynamics.
abstract: Nestin is widely expressed in numerous tumors and has become a diagnostic and prognostic indicator. However, the exact mechanism by which nestin contributes to tumor malignancy remains poorly understood. Here, we found marked upregulation of nestin expression in highly proliferative and invasive gastrointestinal stromal tumor (GIST) specimens. Nestin knockdown in GIST cells reduced the proliferative and invasive activity owing to a decrease of mitochondrial intracellular reactive oxygen species (ROS) generation. Furthermore, nestin was co-localized with mitochondria, and knockdown of nestin increased mitochondrial elongation and influenced the mitochondrial function, including oxygen consumption rates, ATP generation and mitochondrial membrane potential and so on. In exploring the underlying mechanism, we demonstrated nestin knockdown inhibited the mitochondrial recruitment of Dynamin-related protein1 and induced the change of mitochondrial dynamics. Thus, nestin may have an important role in GIST malignancy by regulating mitochondrial dynamics and altering intracellular ROS levels. The findings provide new clues to reveal mechanisms by which nestin mediates the proliferation and invasion of GISTs.
authors.affiliation: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.|Biotherapy Center, Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Cai
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.|Department of Cell Biology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Ke
authors.affiliation: Department of Cardiology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: B
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Gastrointestinal-Pancreatic Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Population Genetics and Prevention, Fuwai Hospital of Peking Union Medical College, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Han
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
authors.forename: C
authors.initials: C
authors.lastname: Lao
authors.affiliation: Department of Gastrointestinal-Pancreatic Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
authors.forename: W
authors.initials: W
authors.lastname: Song
authors.affiliation: Program of Stem Cells and Regenerative Medicine, Affiliated Guangzhou Women and Children's Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.|Biotherapy Center, Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
authors.forename: A P
authors.initials: AP
authors.lastname: Xiang
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D034281:Dynamins; D005260:Female; D020558:GTP Phosphohydrolases / Q000378:metabolism; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism* / Q000473:pathology; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009361:Neoplasm Invasiveness; D064231:Nestin / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection
chemical_list: D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; C577484:NES protein, human; D064231:Nestin; D017382:Reactive Oxygen Species; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins