Dynamin controls extracellular level of Awd/Nme1 metastasis suppressor protein

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Title:	Dynamin controls extracellular level of Awd/Nme1 metastasis suppressor protein
Authors:	徐沺;Romani, Patrizia;Papi, Alessio;Ignesti, Marilena;Soccolini, Giulia;Hsu, Tien;Gargiulo, Giuseppe;Spisni, Enzo;Cavaliere, Valeria
Contributors:	生醫理工學院生醫科學與工程學系
Keywords:	Adipocytes - enzymology;Animals;Animals, Genetically Modified;Biomedical and Life Sciences;Biomedicine;Colonic Neoplasms - enzymology;Colonic Neoplasms - genetics;Drosophila melanogaster - enzymology;Drosophila melanogaster - genetics;Drosophila Proteins - genetics;Drosophila Proteins - metabolism;Dynamin I - genetics;Dynamin I - metabolism;Dynamins - genetics;Dynamins - metabolism;Gene Expression Regulation, Enzymologic;Gene Expression Regulation, Neoplastic;Genotype;HT29 Cells;Humans;Larva - enzymology;Mutation;Neurosciences;NM23 Nucleoside Diphosphate Kinases - genetics;NM23 Nucleoside Diphosphate Kinases - metabolism;Nucleoside-Diphosphate Kinase - genetics;Nucleoside-Diphosphate Kinase - metabolism;Original Article;Pharmacology/Toxicology;Phenotype;RNA Interference;Transfection
Date:	2016-11-01
Issue Date:	2026-04-23 11:15:47 (UTC+8)
Publisher:	Berlin/Heidelberg: Springer Berlin Heidelberg
Abstract:	摘要： Dynamin GTPase (Dyn) plays a critical role in membrane-remodelling events underlying endocytosis. Studies in Drosophila identified a functional interaction between the Dyn homologue, encoded by the shibire ( shi ) gene, and Abnormal wing discs (Awd), a nucleoside diphosphate kinase (NDPK) that is the homologue of group I Nme human genes. These Drosophila studies showed that awd mutations enhance mutant shi phenotype and thus indicated the existence of a highly specific interaction between these genes. Furthermore, in human cells, it has been shown that Nme proteins promote Dyn activity in different membrane compartments through spatially controlled supply of GTP. Interestingly, Awd and Nme proteins have been detected in the extracellular environment. While no role has been inferred to extracellular Awd, presence of Nme1 in cancer patient serum is an unfavourable prognostic marker. In the present work, we used Drosophila and human cell line models to investigate the shuttling Awd/Nme1 proteins between intracellular and extracellular spaces. By using classic and reverse genetic approaches, we show that downregulation of Shi/Dyn1 activity enhances extracellular Awd/Nme1 in both Drosophila and human colon cell lines. We extended our analyses to colon cancer cell lines and found that knocking down Dyn1, besides to raise Nme1 extracellular amount, downregulates expression of molecular components that play key roles in tumour invasion. Interestingly, in vivo analyses of Drosophila larval adipocytes show that the conditional block of Shi activity greatly reduces intracellular amount of Awd confirming that Shi plays a key role in controlling the balance between intracellular and extracellular Awd. 其他題名： Naunyn-Schmiedeberg's Arch Pharmacol 其他題名： Naunyn Schmiedebergs Arch Pharmacol 出版者： Berlin/Heidelberg: Springer Berlin Heidelberg 出版日期： 2016-11 出處： Naunyn-Schmiedeberg's archives of pharmacology, 2016-11, Vol.389 (11), p.1171-1182 版權： Springer-Verlag Berlin Heidelberg 2016 識別號： ISSN: 0028-1298 識別號： EISSN: 1432-1912 識別號： DOI: 10.1007/s00210-016-1268-9 識別號： PMID: 27449069
Appears in Collections:	[Department of Biomedical Sciences and Engineering ] journal & Dissertation

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