title: The zinc transporter LIV-1 is a novel regulator of stemness in pancreatic cancer cells.
abstract: OBJECTIVE
  Recent studies have identified the existence a portion of cancer cells, called "cancer stem cells", within the entire cancer tissue. Cancer stem cells harbor highly tumorigenic and chemo-resistant phenotypes, which lead to recurrence or re-growth of the tumor after surgery. The mechanisms that regulate the stemness of cancer cells remain largely unknown. We hypothesized that LIV-1, a zinc transporter, regulates the stemness in pancreatic cancer cells.
  
  
  METHODS
  We established two stable Panc-1 pancreatic cancer cell lines in which LIV-1 expression was knocked down by the introduction of siRNA against LIV-1. Expression of cancer stem cell-related molecules was examined by quantitative real-time PCR. Expression of ATP-binding cassette sub-family G member 2 was also determined by flow cytometry. Spheroid culture was performed in low-adhesion coated plates. Cell migration was determined by using a modified 2-chamber migration assay. In vivo tumor formation was assessed in nude mice after the subcutaneous injection of cancer cells. The Agilent's miRNA microarray was used to identify differentially expressed miRNAs.
  
  
  RESULTS
  Knockdown of LIV-1 expression resulted in (i) decreased expression of cancer stem cell-related molecules such as LIN28 and ATP-binding cassette sub-family G member 2, (ii) decreased spheroid-forming ability, (iii) decreased migration, (iv) decreased incidence of tumor formation in nude mice, and (v) upregulation of miR-7 expression.
  
  
  CONCLUSIONS
  Our results suggest that LIV-1 might act as a novel regulator of stemness in pancreatic cancer cells.
authors.affiliation: Division of Gastroenterology, Tohoku University Graduate School of Medicine , Sendai , Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Unno
authors.forename: Atsushi
authors.initials: A
authors.lastname: Masamune
authors.forename: Shin
authors.initials: S
authors.lastname: Hamada
authors.forename: Tooru
authors.initials: T
authors.lastname: Shimosegawa
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D015820:Cadherins / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000235:genetics; D018874:Spheroids, Cellular; D015854:Up-Regulation
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015820:Cadherins; D027682:Cation Transport Proteins; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C116614:ABCG2 protein, human; C000715187:Lin28A protein, human; C551557:MIRN149 microRNA, human; C554214:MIRN424 microrna, human; C549242:MIRN7-1 microRNA, human; C418627:SLC39A6 protein, human