| First Author | Upadhyay G | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 19 | Pages | 7820-5 |
| PubMed ID | 21518866 | Mgi Jnum | J:172195 |
| Mgi Id | MGI:5004986 | Doi | 10.1073/pnas.1103441108 |
| Citation | Upadhyay G, et al. (2011) Stem cell antigen-1 enhances tumorigenicity by disruption of growth differentiation factor-10 (GDF10)-dependent TGF-{beta} signaling. Proc Natl Acad Sci U S A 108(19):7820-5 |
| abstractText | Stem cell antigen (Sca)-1/Ly6A, a glycerophosphatidylinositol-linked surface protein, was found to be associated with murine stem cell- and progenitor cell-enriched populations, and also has been linked to the capacity of tumor-initiating cells. Despite these interesting associations, this protein's functional role in these processes remains largely unknown. To identify the mechanism underlying the protein's possible role in mammary tumorigenesis, Sca-1 expression was examined in Sca-1(+/EGFP) mice during carcinogenesis. Mammary tumor cells derived from these mice readily engrafted in syngeneic mice, and tumor growth was markedly inhibited on down-regulation of Sca-1 expression. The latter effect was associated with significantly elevated expression of the TGF-beta ligand growth differentiation factor-10 (GDF10), which was found to selectively activate TGF-beta receptor (TbetaRI/II)-dependent Smad3 phosphorylation. Overexpression of GDF10 attenuated tumor formation; conversely, silencing of GDF10 expression reversed these effects. Sca-1 attenuated GDF10-dependent TGF-beta signaling by disrupting the heterodimerization of TbetaRI and TbetaRII receptors. These findings suggest a new functional role for Sca-1 in maintaining tumorigenicity, in part by acting as a potent suppressor of TGF-beta signaling. |
