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  • Title: Dickkopf-1 (DKK-1) interrupts FAK/PI3K/mTOR pathway by interaction of carbonic anhydrase IX (CA9) in tumorigenesis.
    Author: Kim BR, Shin HJ, Kim JY, Byun HJ, Lee JH, Sung YK, Rho SB.
    Journal: Cell Signal; 2012 Jul; 24(7):1406-13. PubMed ID: 22430125.
    Abstract:
    Recently, we found that carbonic anhydrase IX (CA9) modulates tumor-associated cell migration and invasion, and then identified dickkopf-1 (DKK-1) as a novel CA9-interacting protein. In this study, we have determined the binding regions that are required for interaction between CA9 and DKK-1 through in vitro and in vivo. The N-terminal domain of CA9 is participated to interact with the Val(60)-Tyr(168) site of DKK-1. We also observed that DKK-1 inhibits endothelial cell angiogenesis of CA9 in tumorigenesis. Furthermore, induction of CA9-mediated mTOR phosphorylation and angiogenesis was significantly inhibited by over-expression of DKK-1. Taken together, these findings identify DKK-1 as a potential factor in the regulation of CA9 cellular homeostasis and also suggest a new possible role for DKK1-1 in tumorigenesis.
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