Stem cell antigen-1 (sca-1) regulates mammary tumor development and cell migration

PLoS One. 2011;6(11):e27841. doi: 10.1371/journal.pone.0027841. Epub 2011 Nov 29.


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.

Methodology/principal findings: 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/significance: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / metabolism*
  • Biomarkers, Tumor
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation
  • Collagen Type I / metabolism
  • Collagen Type IV / metabolism
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Fibronectins / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Mammary Neoplasms, Animal / genetics
  • Mammary Neoplasms, Animal / metabolism*
  • Mammary Neoplasms, Animal / pathology*
  • Membrane Proteins / metabolism*
  • Mice
  • RNA, Small Interfering / metabolism
  • Wnt1 Protein / metabolism


  • Antigens, Ly
  • Biomarkers, Tumor
  • Collagen Type I
  • Collagen Type IV
  • Fibronectins
  • Ly6a protein, mouse
  • Membrane Proteins
  • RNA, Small Interfering
  • Wnt1 Protein