QQ客服 官方微博 反馈留言

	Osteopontin promotes gastric cancer metastasis by augmenting cell survival and invasion through Akt-mediated HIF-1α up-regulation and MMP9 activation
	Gang Song ; Gaoliang Ouyang ; Yubin Mao ; Yanlin Ming ; Shideng Bao ; Tianhui Hu
	2009
关键词	Akt gastric cancer HIF-1 alpha MMP9 osteopontin (OPN) survival
英文摘要	Osteopontin (OPN) is a secreted, integrin-binding matrix phosphorylated glycoprotein. OPN has been shown to facilitate the progression and metastasis of malignancies and has prognostic value in several types of cancer, including gastric cancer. However, the functional mechanism of OPN mediated metastatic growth in gastric cancer remains unclear. Here, using multiple in vitro and in vivo models, we report that OPN strongly promoted the progression and metastasis of gastric cancer. Immunohistochemical staining revealed that OPN, matrix metalloproteinase (MMP)9 and hypoxia-inducible factor (HIF)-1 alpha have statistically significant different expression patterns between well- and poorly differentiated tissue samples (P < 0.05). Correlations existed between OPN and MMP9, and between OPN and HIF-1 alpha (r(1) = 0.872, p(1) < 0.01 and r(2) = 0.878, p2 < 0.01). Furthermore, OPN dramatically increased colony formation and invasion of gastric cancer cells in vitro and promoted tumour growth and metastasis in vivo. In addition, OPN potently protected gastric cancer cells from serum depletion-induced apoptosis. Further study shows that OPN activated phosphoinositide 3-kinase/Akt survival pathway and up-regulated HIF-1 alpha via binding to alpha(v)beta(3) integrins in gastric cancer cells. Moreover, we found that OPN could activate MMP9 and up-regulate MMP2. Taken together, our results suggest that the survival-promoting function is crucial for OPN to promote the development of gastric cancer, and HIF-1 alpha and MMP9 may play key roles during this process. Thus, targeting OPN and its related signalling network may develop an effective therapeutic approach for the management of gastric cancer.; National Natural Science Foundation of China [30871242, 30400239, 30570935]; Program for New Century Excellent Talents in Xiamen University ; '985 project' of Xiamen University
语种	英语
出版者	WILEY-BLACKWELL PUBLISHING, INC
内容类型	期刊论文
源URL	[http://dx.doi.org/doi:10.1111/j.1582-4934.2008.00540.x]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Gang Song,Gaoliang Ouyang,Yubin Mao,et al. Osteopontin promotes gastric cancer metastasis by augmenting cell survival and invasion through Akt-mediated HIF-1α up-regulation and MMP9 activation[J],2009.
APA	Gang Song,Gaoliang Ouyang,Yubin Mao,Yanlin Ming,Shideng Bao,&Tianhui Hu.(2009).Osteopontin promotes gastric cancer metastasis by augmenting cell survival and invasion through Akt-mediated HIF-1α up-regulation and MMP9 activation..
MLA	Gang Song,et al."Osteopontin promotes gastric cancer metastasis by augmenting cell survival and invasion through Akt-mediated HIF-1α up-regulation and MMP9 activation".(2009).

个性服务

查看访问统计

相关权益政策

暂无数据

收藏/分享

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。