Abstract
Up-regulation of bone morphogenetic proteins (BMPs) and their receptors by tumor is an important hallmark in cancer progression, as it contributes through autocrine and paracrine mechanisms to tumor development, invasion, and metastasis. Generally, increased motility and invasion are positively correlated with the epithelial-mesenchymal transition (EMT). The purpose of the present study was to determine whether BMP-2 signaling to induce gastric cancer cells to undergo EMT-mediated invasion might pass through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Herein we showed that gastric cancer cell lines express all the components of BMP-2 signaling, albeit to different extents. Moreover, an increased concentration of BMP-2 strongly enhanced motility and invasiveness in gastric cancer cells, whereas no increase was observed in cells treated with either Noggin (a BMP-2 inhibitor) or BMP-2 blocking antibodies. The stimulation of BMP-2 in gastric cancer cells induces a full EMT characterized by Snail induction, E-cadherin delocalization and down-regulation, and up-regulation of mesenchymal and invasiveness markers. Furthermore, blockade of BMP-2 signaling by Noggin or BMP-2 blocking antibodies also restored these changes in EMT markers. In addition, phosphorylation of Akt was also enhanced by treatment with BMP-2, but not Noggin or BMP-2 blocking antibodies. Pretreatment of gastric cancer cells with PI-3 kinase/Akt kinase inhibitor (kinase-dead Akt [DN-Akt], Akt siRNA, or LY294002) significantly inhibited BMP-2-induced EMT and invasiveness. Overall, our studies suggest that BMP-2 promotes motility and invasion of gastric cancer cells by activating PI-3 kinase/Akt and that targeting of this signaling pathway may provide therapeutic opportunities in preventing metastasis mediated by BMP-2.
| Original language | English |
|---|---|
| Pages (from-to) | 24-37 |
| Number of pages | 14 |
| Journal | Experimental Cell Research |
| Volume | 316 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2010 Jan 1 |
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Keywords
- Bone morphogenetic protein-2 (BMP-2)
- Epithelial-mesenchymal transition (EMT)
- Invasion
- Metastasis
- Migration
- Phosphatidylinositol 3-kinase (PI3K)/Akt
ASJC Scopus subject areas
- Cell Biology
Cite this
BMP2 accelerates the motility and invasiveness of gastric cancer cells via activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. / Kang, Myoung Hee; Kim, Jun Suk; Seo, Ji Eun; Oh, Sang Cheul; Yoo, Young A.
In: Experimental Cell Research, Vol. 316, No. 1, 01.01.2010, p. 24-37.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - BMP2 accelerates the motility and invasiveness of gastric cancer cells via activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway
AU - Kang, Myoung Hee
AU - Kim, Jun Suk
AU - Seo, Ji Eun
AU - Oh, Sang Cheul
AU - Yoo, Young A.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Up-regulation of bone morphogenetic proteins (BMPs) and their receptors by tumor is an important hallmark in cancer progression, as it contributes through autocrine and paracrine mechanisms to tumor development, invasion, and metastasis. Generally, increased motility and invasion are positively correlated with the epithelial-mesenchymal transition (EMT). The purpose of the present study was to determine whether BMP-2 signaling to induce gastric cancer cells to undergo EMT-mediated invasion might pass through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Herein we showed that gastric cancer cell lines express all the components of BMP-2 signaling, albeit to different extents. Moreover, an increased concentration of BMP-2 strongly enhanced motility and invasiveness in gastric cancer cells, whereas no increase was observed in cells treated with either Noggin (a BMP-2 inhibitor) or BMP-2 blocking antibodies. The stimulation of BMP-2 in gastric cancer cells induces a full EMT characterized by Snail induction, E-cadherin delocalization and down-regulation, and up-regulation of mesenchymal and invasiveness markers. Furthermore, blockade of BMP-2 signaling by Noggin or BMP-2 blocking antibodies also restored these changes in EMT markers. In addition, phosphorylation of Akt was also enhanced by treatment with BMP-2, but not Noggin or BMP-2 blocking antibodies. Pretreatment of gastric cancer cells with PI-3 kinase/Akt kinase inhibitor (kinase-dead Akt [DN-Akt], Akt siRNA, or LY294002) significantly inhibited BMP-2-induced EMT and invasiveness. Overall, our studies suggest that BMP-2 promotes motility and invasion of gastric cancer cells by activating PI-3 kinase/Akt and that targeting of this signaling pathway may provide therapeutic opportunities in preventing metastasis mediated by BMP-2.
AB - Up-regulation of bone morphogenetic proteins (BMPs) and their receptors by tumor is an important hallmark in cancer progression, as it contributes through autocrine and paracrine mechanisms to tumor development, invasion, and metastasis. Generally, increased motility and invasion are positively correlated with the epithelial-mesenchymal transition (EMT). The purpose of the present study was to determine whether BMP-2 signaling to induce gastric cancer cells to undergo EMT-mediated invasion might pass through the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. Herein we showed that gastric cancer cell lines express all the components of BMP-2 signaling, albeit to different extents. Moreover, an increased concentration of BMP-2 strongly enhanced motility and invasiveness in gastric cancer cells, whereas no increase was observed in cells treated with either Noggin (a BMP-2 inhibitor) or BMP-2 blocking antibodies. The stimulation of BMP-2 in gastric cancer cells induces a full EMT characterized by Snail induction, E-cadherin delocalization and down-regulation, and up-regulation of mesenchymal and invasiveness markers. Furthermore, blockade of BMP-2 signaling by Noggin or BMP-2 blocking antibodies also restored these changes in EMT markers. In addition, phosphorylation of Akt was also enhanced by treatment with BMP-2, but not Noggin or BMP-2 blocking antibodies. Pretreatment of gastric cancer cells with PI-3 kinase/Akt kinase inhibitor (kinase-dead Akt [DN-Akt], Akt siRNA, or LY294002) significantly inhibited BMP-2-induced EMT and invasiveness. Overall, our studies suggest that BMP-2 promotes motility and invasion of gastric cancer cells by activating PI-3 kinase/Akt and that targeting of this signaling pathway may provide therapeutic opportunities in preventing metastasis mediated by BMP-2.
KW - Bone morphogenetic protein-2 (BMP-2)
KW - Epithelial-mesenchymal transition (EMT)
KW - Invasion
KW - Metastasis
KW - Migration
KW - Phosphatidylinositol 3-kinase (PI3K)/Akt
UR - http://www.scopus.com/inward/record.url?scp=70449713259&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70449713259&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2009.10.010
DO - 10.1016/j.yexcr.2009.10.010
M3 - Article
C2 - 19835871
AN - SCOPUS:70449713259
VL - 316
SP - 24
EP - 37
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 1
ER -