Regulation of Lung Cancer Cell Migration and Invasion by Reactive Oxygen Species and Caveolin-1
Regulation of Lung Cancer Cell Migration and Invasion by Reactive Oxygen Species and Caveolin-1
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DOI：
10.1074/jbc.m110.124958
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发表时间：
2010-12-01
影响因子：
4.8
通讯作者：
Chanvorachote, Pithi
中科院分区：
文献类型：
--
作者：
Luanpitpong, Sudjit;Talbott, Siera Jo;Chanvorachote, Pithi
肿瘤细胞迁移和侵袭邻近组织的获得性能力与高转移潜力和晚期癌症有关。最近，信号分子如活性氧（ROS）和小窝蛋白-1 （Cav-1）被认为与癌细胞的攻击行为有关。然而，特异性ROS在癌细胞迁移和Cav-1调控中的作用尚不清楚。我们在这里证明了Cav-1在人肺癌H460细胞的迁移和侵袭中起重要作用，并且这些作用受到细胞ROS的差异调节。利用各种已知的ROS抑制剂和供体，我们发现不同的ROS对Cav-1表达和细胞迁移和侵袭有不同的影响。超氧阴离子和过氧化氢下调Cav-1表达，抑制细胞迁移和侵袭，羟基自由基上调Cav-1表达，促进细胞迁移和侵袭。超氧阴离子和过氧化氢对Cav-1的下调作用是通过一种转录不依赖的机制介导的，该机制通过泛素-蛋白酶体途径介导蛋白质降解。这些结果表明，不同的ROS在癌细胞运动中发挥重要作用，并通过Cav-1的表达，可能提供了控制肿瘤进展和转移的关键机制。羟基自由基对Cav-1和细胞运动的上调提示了这种ROS作为肿瘤进展的积极调节因子的重要作用。
The acquired capability of tumor cells to migrate and invade neighboring tissues is associated with high metastatic potential and advanced stage of cancers. Recently, signaling molecules such as reactive oxygen species (ROS) and caveolin-1 (Cav-1) have been implicated in the aggressive behavior of cancer cells. However, the roles of specific ROS in cancer cell migration and Cav-1 regulation are unclear. We demonstrate here that Cav-1 plays an important role in the migration and invasion of human lung carcinoma H460 cells and that these effects are differentially regulated by cellular ROS. Using various known inhibitors and donors of ROS, we found that different ROS have different effects on Cav-1 expression and cell migration and invasion. Superoxide anion and hydrogen peroxide down-regulated Cav-1 expression and inhibited cell migration and invasion, whereas hydroxyl radical up-regulated the Cav-1 expression and promoted cell migration and invasion. The down-regulating effect of superoxide anion and hydrogen peroxide on Cav-1 is mediated through a transcription-independent mechanism that involves protein degradation via the ubiquitin-proteasome pathway. These results indicate the essential role of different ROS in cancer cell motility and through Cav-1 expression, which may provide a key mechanism controlling tumor progression and metastasis. The upregulation of Cav-1 and cell motility by hydroxyl free radical suggests an important role of this ROS as a positive regulator of tumor progression.