Tumor Biology

, Volume 36, Issue 12, pp 9475–9486 | Cite as

BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation

  • Bo Ram Kim
  • Sang Cheul Oh
  • Dae-Hee Lee
  • Jung Lim Kim
  • Suk Young Lee
  • Myoung Hee Kang
  • Sun Il Lee
  • Sanghee Kang
  • Sung Yup Joung
  • Byung Wook Min
Research Article


Bone morphogenetic proteins (BMPs) have been involved in metastatic progression and tumorigenesis of many cancer types. However, it remains unclear how BMP-2 contributes to the initiation and development of these cancers. Here, we investigated the role of BMP-2 in colon cancer stem cell (CSC) development from colon cancer cells. We also determined the effects of BMP-2 on CSC development and epithelial-mesenchymal transition (EMT) in human colon cancer cell lines HCT-116 and SW620. We found that BMP-2 enhanced sphere formation of colon cancer cells without serum. Also, BMP-2-induced spheres displayed up-regulation of stemness markers (CD133+ and EpCAM+) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activators p-Smad1/5 and Snail and N-cadherin was increased in the spheres’ cells, indicating that BMP-2 signaling might result in CSC self-renewal and EMT. Furthermore, siRNA-mediated knockdown of signal transducer and activator of transcription 3 (STAT3) in HCT-116 cells reversed BMP-2-induced EMT and stem cell formation. Taken together, our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in CSC markers.


Colon cancer Bone morphogenetic proteins Cancer stem cells Epithelial-mesenchymal transition Signal transducer and activator of transcription 3 



This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF2012R1A1A2042905) and supported by Korea University Grant (K1421591).

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Bo Ram Kim
    • 1
  • Sang Cheul Oh
    • 2
  • Dae-Hee Lee
    • 2
  • Jung Lim Kim
    • 2
  • Suk Young Lee
    • 2
  • Myoung Hee Kang
    • 3
  • Sun Il Lee
    • 4
  • Sanghee Kang
    • 4
  • Sung Yup Joung
    • 4
  • Byung Wook Min
    • 4
  1. 1.Graduate School of MedicineKorea University College of MedicineSeoulRepublic of Korea
  2. 2.Division of Oncology/Hematology, Department of Internal MedicineKorea University College of MedicineSeoulRepublic of Korea
  3. 3.University of Ulsan College of MedicineAsan Institute for Life ScienceSeoulRepublic of Korea
  4. 4.Department of Surgery, Korea University Guro HospitalKorea University College of MedicineSeoulRepublic of Korea

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