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学科主题: 基础医学
题名:
Phosphoprotein associated with glycosphingolipid microdomains 1 inhibits the proliferation and invasion of human prostate cancer cells in vitro through suppression of Ras activation
作者: Yu, Wenjuan1,2; Wang, Yuewei3; Gong, Miaozi1; Pei, Fei1; Zheng, Jie1
关键词: prostate cancer ; cancer metastasis ; gene ; PAG ; RasGAP
刊名: ONCOLOGY REPORTS
发表日期: 2012-08-01
DOI: 10.3892/or.2012.1848
卷: 28, 期:2, 页:606-614
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: TERMINAL SRC KINASE ; ENRICHED MICRODOMAINS ; PROTEIN ; CSK ; CYTOSKELETON ; RAFTS ; PAG
英文摘要:

Phosphoprotein associated with glycosphingolipid microdomains 1 (PAG) is an important negative regulator of immune signaling in T lymphocytes. However, newly emerging evidence has indicated that PAG may play important roles in tumor cells. Our previously reported cDNA microarray experiments identified PAG as a gene down-regulated in the high metastatic potential prostate cancer cell line PC-3M-1E8. In this study, we investigated the role of PAG in the proliferation, invasion and metastasis of prostate cancer cells and the underlying mechanisms. We confirmed that the expression of PAG at both the mRNA and protein levels was low in PC-3M-1E8 and DU145 cells compared to low metastatic potential prostate cancer cells PC-3M-2B4. In addition, we demonstrated that the reintroduction of PAG to PC-3M-1E8 and DU145 cells led to reduced proliferation through cell cycle arrest, decreased anchorage-independent growth and reduced invasion ability of tumor cells in vitro. This is the first report demonstrating that PAG inhibits the proliferation and invasion potential of prostate cancer cells via the interaction with RasGAP to recruit RasGAP to the cell membrane, where RasGAP hydrolyzes GTP to GDP, reduces the level of activated Ras, and ultimately suppresses the activation of ERK1/2, cyclin D1 and other effectors of the Ras signaling pathway. Morphologically, we observed that PAG could diminish the formation of pseudopodia on the cell surface and redistribute the intracellular F-actin in PC-3M-1E8 cells, which directly leads to the decreased invasion and metastasis potential of tumor cells. Taken together, these results suggest that PAG acts to inhibit the development and metastasis of prostate cancers and represents a novel therapeutic target for prostate cancer.

语种: 英语
所属项目编号: 2009CB521805
项目资助者: Nation 973 basal research development assistance programs of China
WOS记录号: WOS:000306160400028
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67301
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100191, Peoples R China
2.Qingdao Univ, Coll Med, Affiliated Hosp, Dept Pathol, Qingdao 266071, Peoples R China
3.Qingdao Univ, Coll Med, Affiliated Hosp, Dept Vasc Surg, Qingdao 266071, Peoples R China

Recommended Citation:
Yu, Wenjuan,Wang, Yuewei,Gong, Miaozi,et al. Phosphoprotein associated with glycosphingolipid microdomains 1 inhibits the proliferation and invasion of human prostate cancer cells in vitro through suppression of Ras activation[J]. ONCOLOGY REPORTS,2012,28(2):606-614.
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