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学科主题: 临床医学
题名:
BMPR2 inhibition induced apoptosis and autophagy via destabilization of XIAP in human chondrosarcoma cells
作者: Jiao, G.1; Guo, W.1; Ren, T.1; Lu, Q.1; Sun, Y.1; Liang, W.1; Ren, C.1; Yang, K.1; Sun, K.2
刊名: CELL DEATH & DISEASE
发表日期: 2014-12-01
DOI: 10.1038/cddis.2014.540
卷: 5
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: MORPHOGENETIC PROTEIN-RECEPTOR ; PROSTATE-CANCER CELLS ; X-LINKED INHIBITOR ; BONE ; EXPRESSION ; GROWTH ; FAMILY ; GENES ; DEATH ; DEGRADATION
英文摘要:

Bone morphogenetic proteins (BMPs) are multifunctional proteins, and their receptors (BMPRs) have crucial roles in the process of signaling. However, their function in cancer is somewhat inconsistent. It has been demonstrated that more prevalent expression of bone morphogenetic protein receptor 2 (BMPR2) has been detected in dedifferentiated chondrosarcomas than conventional chondrosarcomas. Here, we find that BMPR2 inhibition induces apoptosis and autophagy of chondrosarcoma. We found that BMPR2 expression was correlated with the clinicopathological features of chondrosarcomas, and could predict the treatment outcome. Knockdown of BMPR2 by small interfering RNA results in growth inhibition in chondrosarcoma cells. Silencing BMPR2 promoted G2/M cell cycle arrest, induced chondrosarcoma cell apoptosis through caspase-3-dependent pathway via repression of X-linked inhibitor of apoptosis protein (XIAP) and induced autophagy of chondrosarcoma cells via XIAP-Mdm2-p53 pathway. Inhibition of autophagy induced by BMPR2 small interfering RNA (siBMPR2) sensitized chondrosarcoma cells to siBMPR2-induced apoptotic cell death, suggesting that autophagy has a protective role for chondrosarcoma cells in context of siBMPR2-induced apoptotic cell death. In vivo tumorigenicity assay in mice indicated that inhibition of BMPR2 reduced tumor growth. Taken together, our results suggest that BMPR2 has a significant role in the tumorigenesis of chondrosarcoma, and could be an important prognostic marker for chondrosarcoma. BMPR2 inhibition could eventually provide a promising therapy for chondrosarcoma treatment.

语种: 英语
所属项目编号: 81172543 ; 20130001110076
项目资助者: Natural Science Foundation of China ; Specialised Research Fund for the Doctoral Programme of Higher Education of China
WOS记录号: WOS:000347837400024
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/60837
Appears in Collections:北京大学第二临床医学院_骨肿瘤科_期刊论文

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作者单位: 1.Peking Univ, Peoples Hosp, Musculoskeletal Tumor Ctr, Beijing 100044, Peoples R China
2.Peking Univ, Peoples Hosp, Dept Pathol, Beijing 100044, Peoples R China

Recommended Citation:
Jiao, G.,Guo, W.,Ren, T.,et al. BMPR2 inhibition induced apoptosis and autophagy via destabilization of XIAP in human chondrosarcoma cells[J]. CELL DEATH & DISEASE,2014,5.
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