title: Bone morphogenetic protein 2 mediates epithelial-mesenchymal transition via AKT and ERK signaling pathways in gastric cancer.
abstract: Although deregulation of bone morphogenetic protein 2 (BMP2) signaling has been linked to various types of cancers, the relationships between abnormal activation of these signaling pathways and tumorigenesis are not clear in gastric cancer. We hypothesized that BMP2 might be involved in epithelial-mesenchymal transition (EMT) process of gastric cancer. Here, BMPR-II activation and inhibition in gastric cancer cell line AGS were induced with exogenous BMP2 and with BMPR-II small interfering RNA (siRNA), respectively. BMPR-II downstream signal molecules AKT, ERK phosphorylation, and EMT biomarkers (vimentin, snail, N-cadherin, and E-cadherin) were tested using the Western blot. In the present study, our results showed that BMP2 can induce AKT and ERK phosphorylation in a dose-dependent method, and endogenous BMPR-II can be inhibited completely by BMPR-II siRNA in AGS. Notably BMP2 alone treatment can induce the up-regulation of vimentin, snail, and N-cadherin in AGS cells, besides, the down-regulation of E-cadherin also occurred. On the contrary, BMPR-II siRNA significantly prohibited BMP2-induced AKT and ERK phosphorylation, at the same time, EMT biomarkers changes were not observed. On the other hand, BMPR-II knockdown could significantly affect AGS wound closure and the migration ability (p < 0.001) compared to control siRNA and BMP2 alone. In conclusion, this study suggested that EMT process can be triggered by the BMP2/BMPR axis in gastric cancer and then involved in the tumor cell migration, invasion, and metastasis via the activation of PI3K/AKT and MEK/ERK pathways. Our study lays a new foundation for the treatment of gastric cancer through antagonizing BMP2 system.
authors.affiliation: Department of Radiation Oncology, Peking University 3rd Hospital, Beijing,, 100191, China, liaoanyan323@126.com.
authors.forename: Anyan
authors.initials: A
authors.lastname: Liao
authors.forename: Weijie
authors.initials: W
authors.lastname: Wang
authors.forename: Dawei
authors.initials: D
authors.lastname: Sun
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Jiang
authors.forename: Suqing
authors.initials: S
authors.lastname: Tian
authors.forename: Jinna
authors.initials: J
authors.lastname: Li
authors.forename: Xiangshan
authors.initials: X
authors.lastname: Yang
authors.forename: Ranran
authors.initials: R
authors.lastname: Shi
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D051057:Proto-Oncogene Proteins c-akt