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

Boh-Ram Kim; Hye-Jin Shin; Joo-Young Kim; Hyun-Jung Byun; Jeong Heon Lee; Young Kwan Sung; Seung Bae Rho

doi:10.1016/j.cellsig.2012.03.002

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

Cell Signal. 2012 Jul;24(7):1406-13. doi: 10.1016/j.cellsig.2012.03.002. Epub 2012 Mar 10.

Authors

Boh-Ram Kim¹, Hye-Jin Shin, Joo-Young Kim, Hyun-Jung Byun, Jeong Heon Lee, Young Kwan Sung, Seung Bae Rho

Affiliation

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

PMID: 22430125
DOI: 10.1016/j.cellsig.2012.03.002

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antigens, Neoplasm / genetics
Antigens, Neoplasm / metabolism*
Carbonic Anhydrase IX
Carbonic Anhydrases / genetics
Carbonic Anhydrases / metabolism*
Cell Movement
Cell Proliferation
Cell Transformation, Neoplastic / genetics
Cell Transformation, Neoplastic / metabolism
Endothelial Cells / cytology
Endothelial Cells / metabolism
Focal Adhesion Kinase 1 / metabolism
HeLa Cells
Human Umbilical Vein Endothelial Cells
Humans
Intercellular Signaling Peptides and Proteins / genetics
Intercellular Signaling Peptides and Proteins / metabolism*
Neovascularization, Pathologic / genetics
Neovascularization, Pathologic / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Phosphorylation
Protein Binding
Protein Interaction Domains and Motifs
Protein Structure, Tertiary
Signal Transduction
TOR Serine-Threonine Kinases / metabolism
Vascular Endothelial Growth Factor A / metabolism

Substances

Antigens, Neoplasm
DKK1 protein, human
Intercellular Signaling Peptides and Proteins
VEGFA protein, human
Vascular Endothelial Growth Factor A
MTOR protein, human
Focal Adhesion Kinase 1
PTK2 protein, human
TOR Serine-Threonine Kinases
CA9 protein, human
Carbonic Anhydrase IX
Carbonic Anhydrases