Upregulated expression of periostin by hypoxia in non-small-cell lung cancer cells promotes cell survival via the Akt/PKB pathway
Upregulated expression of periostin by hypoxia in non-small-cell lung cancer cells promotes cell survival via the Akt/PKB pathway
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非小细胞肺癌细胞缺氧导致骨膜素表达上调，通过 Akt/PKB 途径促进细胞存活
DOI：
10.1016/j.canlet.2009.02.030
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发表时间：
2009-08-28
期刊：
影响因子：
9.7
通讯作者：
Bao, Shideng
中科院分区：
文献类型：
--
作者：
Ouyang, Gaoliang;Liu, Min;Bao, Shideng
骨膜蛋白是一种分泌蛋白，在各种类型的人类癌症中经常过度表达。我们之前报道过，通过增加细胞存活，骨膜蛋白能有效促进结肠癌的转移性生长。然而，人们对骨膜蛋白在非小细胞肺癌中的作用知之甚少。本研究发现，非小细胞肺癌A549细胞中periostin的表达增加是对化学模拟缺氧应激的一种细胞反应，这种作用可能受缺氧诱导因子tgf - α和bFGF的调控。我们进一步证明，tgf - α和bFGF激活RTK/PI3-K通路上调骨膜蛋白的表达，进而骨膜蛋白通过激活Akt/PKB通路促进缺氧微环境下A549细胞的存活。因此，骨膜蛋白及其参与的途径可能为肺癌的治疗提供一个靶点。2009爱思唯尔爱尔兰有限公司版权所有。
Periostin is a secreted protein and has been shown to be frequently overexpressed in various types of human cancers. We have previously reported that periostin potently promotes metastatic growth of colon cancer by augmenting cell survival. However, little is known about the functions of periostin in non-small-cell lung cancer. Here, we revealed that increased expression of periostin in non-small-cell lung cancer A549 cells was one kind of cellular responses to the stress of chemical-mimic hypoxia, and this effect could be regulated by hypoxia inducible growth factors, such as TGF-alpha and bFGF. We further demonstrated that RTK/PI3-K pathway activated by TGF-alpha and bFGF was evoked in upregulating the expression of periostin, and then periostin promoted the survival of A549 cells under hypoxic microenvironment via activation of Akt/PKB pathway. Therefore, periostin and the pathway that it involved might provide a target for lung cancer treatment. (C) 2009 Elsevier Ireland Ltd. All rights reserved.