title: Stem cell antigen-1 (sca-1) regulates mammary tumor development and cell migration.
abstract: BACKGROUND
  Stem cell antigen-1 (Sca-1 or Ly6A) is a glycosyl phostidylinositol (GPI)-anchored cell surface protein associated with both stem and progenitor activity, as well as tumor initiating-potential. However, at present the functional role for Sca-1 is poorly defined.
  
  
  RESULTS
  To investigate the role of Sca-1 in mammary tumorigenesis, we used a mammary cell line derived from a MMTV-Wnt1 mouse mammary tumor that expresses high levels of endogenous Sca-1. Using shRNA knockdown, we demonstrate that Sca-1 expression controls cell proliferation during early tumor progression in mice. Functional limiting dilution transplantations into recipient mice demonstrate that repression of Sca-1 increases the population of tumor propagating cells. In scratch monolayer assays, Sca-1 enhances cell migration. In addition, knockdown of Sca-1 was shown to affect cell adhesion to a number of different extracellular matrix components. Microarray analysis indicates that repression of Sca-1 leads to changes in expression of genes involved in proliferation, cell migration, immune response and cell organization.
  
  
  CONCLUSIONS
  Sca-1 exerts marked effects on cellular activity and tumorgenicity both in vitro and in vivo. A better understanding of Sca-1 function may provide insight into the broader role of GPI-anchored cell surface proteins in cancer.
authors.affiliation: Interdepartmental Program in Cell & Molecular Biology, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Torey D
authors.initials: TD
authors.lastname: Batts
authors.forename: Heather L
authors.initials: HL
authors.lastname: Machado
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Creighton
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Rosen
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D014408:Biomarkers, Tumor; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D034741:RNA, Small Interfering / Q000378:metabolism; D051155:Wnt1 Protein / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; D014408:Biomarkers, Tumor; D024042:Collagen Type I; D024141:Collagen Type IV; D005353:Fibronectins; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051155:Wnt1 Protein