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

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

Department of Medicine

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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 Val⁶⁰-Tyr¹⁶⁸ 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.

Original language	English
Pages (from-to)	1406-1413
Number of pages	8
Journal	Cellular Signalling
Volume	24
Issue number	7
DOIs	https://doi.org/10.1016/j.cellsig.2012.03.002
State	Published - Jul 2012

Keywords

Angiogenesis
Apoptosis
CA9
DKK-1
Protein-protein interaction
Tumorigenesis
Yeast two-hybrid

Access to Document

10.1016/j.cellsig.2012.03.002

Cite this

@article{0bc4bc698b934201aa9fa966a7328c7d,

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

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 Val60-Tyr168 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.",

keywords = "Angiogenesis, Apoptosis, CA9, DKK-1, Protein-protein interaction, Tumorigenesis, Yeast two-hybrid",

author = "Kim, {Boh Ram} and Shin, {Hye Jin} and Kim, {Joo Young} and Byun, {Hyun Jung} and Lee, {Jeong Heon} and Sung, {Young Kwan} and Rho, {Seung Bae}",

year = "2012",

month = jul,

doi = "10.1016/j.cellsig.2012.03.002",

language = "English",

volume = "24",

pages = "1406--1413",

journal = "Cellular Signalling",

issn = "0898-6568",

publisher = "Elsevier Inc.",

number = "7",

}

TY - JOUR

T1 - Dickkopf-1 (DKK-1) interrupts FAK/PI3K/mTOR pathway by interaction of carbonic anhydrase IX (CA9) in tumorigenesis

AU - Kim, Boh Ram

AU - Shin, Hye Jin

AU - Kim, Joo Young

AU - Byun, Hyun Jung

AU - Lee, Jeong Heon

AU - Sung, Young Kwan

AU - Rho, Seung Bae

PY - 2012/7

Y1 - 2012/7

N2 - 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 Val60-Tyr168 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.

AB - 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 Val60-Tyr168 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.

KW - Angiogenesis

KW - Apoptosis

KW - CA9

KW - DKK-1

KW - Protein-protein interaction

KW - Tumorigenesis

KW - Yeast two-hybrid

UR - http://www.scopus.com/inward/record.url?scp=84860003307&partnerID=8YFLogxK

U2 - 10.1016/j.cellsig.2012.03.002

DO - 10.1016/j.cellsig.2012.03.002

M3 - Article

C2 - 22430125

AN - SCOPUS:84860003307

SN - 0898-6568

VL - 24

SP - 1406

EP - 1413

JO - Cellular Signalling

JF - Cellular Signalling

IS - 7

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this