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Dickkopf-1 (DKK-1) interrupts FAK/PI3K/mTOR pathway by interaction of carbonic anhydrase IX (CA9) in tumorigenesis

Boh-Ram Kim1, Hye-Jin Shin, Joo-Young Kim

  • 1Research Institute and Hospital, National Cancer Center, Ilsandong-gu, Goyang-si, Gyeonggi-do, Republic of Korea.

Cellular Signalling
|March 21, 2012
PubMed

Insights

Dickkopf-1 (DKK-1) interacts with carbonic anhydrase IX (CA9) at its N-terminal domain, inhibiting CA9-driven tumor cell migration and angiogenesis. This interaction highlights DKK-1

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Carbonic anhydrase IX (CA9) is implicated in tumor cell migration and invasion.
  • Dickkopf-1 (DKK-1) has been identified as a novel protein interacting with CA9.

Purpose of the Study:

  • To determine the specific binding regions between CA9 and DKK-1.
  • To investigate the functional consequences of the CA9-DKK-1 interaction on tumorigenesis and angiogenesis.

Main Methods:

  • In vitro and in vivo binding assays to identify interaction sites.
  • Over-expression studies to assess the functional impact of DKK-1 on CA9 activity.
  • Analysis of CA9-mediated mTOR phosphorylation and angiogenesis.

Main Results:

  • The N-terminal domain of CA9 interacts with the Val(60)-Tyr(168) site of DKK-1.
  • DKK-1 inhibits CA9-driven endothelial cell angiogenesis in tumorigenesis.
  • Over-expression of DKK-1 significantly inhibits CA9-mediated mTOR phosphorylation and angiogenesis.

Conclusions:

  • DKK-1 acts as a regulator of CA9 cellular homeostasis.
  • DKK-1 plays a potential role in inhibiting tumorigenesis by modulating CA9 activity.

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