Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 280, Issue 14, Pages 13641-13647Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M413047200
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Lipocalin 2, an iron-siderophore-binding protein, converts embryonic kidney mesenchyme to epithelia. We found that lipocalin 2 could also convert 4T1-Ras-transformed mesenchymal tumor cells to an epithelial phenotype, increase E-cadherin expression, and suppress cell invasiveness in vitro and tumor growth and lung metastases in vivo. The Ras-MAPK pathway mediated the epithelial to mesenchymal transition in part by increasing E-cadherin phosphorylation and degradation. Lipocalin 2 antagonized these effects at a point upstream of Raf activation. Lipocalin 2 action was enhanced by iron-siderophore. These data characterize lipocalin 2 as an epithelial inducer in Ras malignancy and a suppressor of metastasis.
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