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Updated: Jun 21, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Inhibition of PI3 kinase/Akt pathway is required for BMP2-induced EMT and invasion
Myoung Hee Kang1, Han Na Kang, Jung Lim Kim
1Graduate School of Medicine, Department of Internal Medicine, Korea University College of Medicine, Korea University, Seoul 136-705, Korea.
Abstract:
Although dysregulation of bone morphogenetic protein (BMP) signaling has been linked to various types of cancers, the relationship between abnormal activation of these signaling pathways and tumorigenesis is not clear. The purpose of the current study was to clarify how BMP2 is involved in colon cancer aggressiveness. The data showed that SW480 and DLD-1 cells displayed different responses to short- and long-term exposure to BMP2. During the first 24 h of exposure to BMP2, these cells were growth-inhibited, whereas surviving cells became resistant to growth inhibition, showing epithelial-to-mesenchymal transformation (EMT) and enhanced motility and invasiveness. Interestingly, in highly metastatic mesenchymal colon carcinoma cells (CT26), blockade of BMP2 signaling by BMP2 siRNA prevented EMT, motility and invasiveness; rather, blockade of BMP2 signaling caused a mesenchymal-to-epithelial transition (MET). The levels of phosphorylated Akt were very different between the two cell types; the BMP2-sensitive SW480 and DLD-1 cells had much higher levels of expression than the BMP2-resistant SW480 and DLD-1 and CT26 cells. CT26 cells, following exposure to BMP2 and activation of Akt, escaped the EMT-induced cellular motility and invasiveness. Moreover, LY294002 treatment of BMP2-sensitive SW480 cells blocked cell growth and enhanced motility and invasiveness. Together, these results suggest that suppression of the PI3 kinase/Akt pathway is correlated with the development of BMP2 resistance and invasion in BMP2-induced EMT in colon cancer.
Insights
Bone morphogenetic protein 2 (BMP2) initially inhibits colon cancer cell growth but promotes epithelial-to-mesenchymal transformation (EMT), enhancing invasiveness. Suppression of the PI3 kinase/Akt pathway correlates with BMP2 resistance and invasion.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Dysregulated bone morphogenetic protein (BMP) signaling is implicated in various cancers.
- The precise role of BMP signaling in colon cancer tumorigenesis and aggressiveness remains unclear.
Purpose of the Study:
- To elucidate the involvement of BMP2 in colon cancer aggressiveness.
- To investigate the mechanisms underlying BMP2-induced changes in colon cancer cells.
Main Methods:
- Exposure of colon cancer cell lines (SW480, DLD-1, CT26) to BMP2.
- Utilized BMP2 siRNA to block BMP2 signaling.
- Investigated epithelial-to-mesenchymal transformation (EMT), motility, and invasiveness.
- Assessed levels of phosphorylated Akt.
- Employed LY294002 (PI3K inhibitor) treatment.
Main Results:
- Short-term BMP2 exposure inhibited SW480/DLD-1 cell growth; long-term exposure induced resistance, promoting EMT, motility, and invasiveness.
- BMP2 blockade in CT26 cells prevented EMT and invasiveness, inducing mesenchymal-to-epithelial transition (MET).
- BMP2-sensitive SW480/DLD-1 cells showed higher phosphorylated Akt levels than resistant cells and CT26 cells.
- BMP2 and Akt activation in CT26 cells led to escape from EMT-induced invasiveness.
- LY294002 treatment of BMP2-sensitive cells blocked growth and enhanced motility/invasiveness.
Conclusions:
- BMP2 plays a dual role in colon cancer, initially inhibiting growth then promoting aggressive phenotypes via EMT.
- Suppression of the PI3 kinase/Akt pathway is linked to BMP2 resistance and increased invasion in BMP2-induced EMT.
- Targeting the PI3K/Akt pathway could be a strategy for managing BMP2-driven colon cancer progression.
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