title: BMP-2 induces motility and invasiveness by promoting colon cancer stemness through STAT3 activation.
abstract: 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.
authors.affiliation: Graduate School of Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Bo Ram
authors.initials: BR
authors.lastname: Kim
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang Cheul
authors.initials: SC
authors.lastname: Oh
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Dae-Hee
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jung Lim
authors.initials: JL
authors.lastname: Kim
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea.
authors.forename: Suk Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: University of Ulsan College of Medicine, Asan Institute for Life Science, Seoul, Republic of Korea.
authors.forename: Myoung Hee
authors.initials: MH
authors.lastname: Kang
authors.affiliation: Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-gil, Guro-gu, Seoul, 152-703, Republic of Korea.
authors.forename: Sun Il
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-gil, Guro-gu, Seoul, 152-703, Republic of Korea.
authors.forename: Sanghee
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-gil, Guro-gu, Seoul, 152-703, Republic of Korea.
authors.forename: Sung Yup
authors.initials: SY
authors.lastname: Joung
authors.affiliation: Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148 Gurodong-gil, Guro-gu, Seoul, 152-703, Republic of Korea. gsmin@korea.ac.kr.
authors.forename: Byung Wook
authors.initials: BW
authors.lastname: Min
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D000071858:Epithelial Cell Adhesion Molecule; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells; D010455:Peptides / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000951:Antigens, Neoplasm; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: Bone morphogenetic proteins; Cancer stem cells; Colon cancer; Epithelial-mesenchymal transition; Signal transducer and activator of transcription 3