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Lipocalin 2 diminishes invasiveness and metastasis of Ras-transformed cells.

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.[1]


  1. Lipocalin 2 diminishes invasiveness and metastasis of Ras-transformed cells. Hanai, J., Mammoto, T., Seth, P., Mori, K., Karumanchi, S.A., Barasch, J., Sukhatme, V.P. J. Biol. Chem. (2005) [Pubmed]
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