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.

Oncology Reports
|July 30, 2009
PubMed

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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