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Regulation of lung cancer cell migration and invasion by reactive oxygen species and caveolin-1.

Authors
Luanpitpong-S; Talbott-SJ; Rojanasakul-Y; Nimmannit-U; Pongrakhananon-V; Wang-LY; Chanvorachote-P
Source
J Biol Chem 2010 Dec; 285(50):38832-38840
NIOSHTIC No.
20038082
Abstract
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 up-regulation of Cav-1 and cell motility by hydroxyl free radical suggests an important role of this ROS as a positive regulator of tumor progression.
Keywords
Cancer; Lung-cancer; Lung-cells; Tumors; Cell-alteration; Cell-damage; Cell-migration; Tissue-culture; Molecular-biology; Cell-biology; Cell-function; Carcinomas; Antitumor-agents; Hydrogen-ion-activity; Hydroxyl-groups; Protein-biochemistry; Proteins; Free-radicals
CODEN
JBCHA3
Publication Date
20101210
Document Type
Journal Article
Email Address
yrojan@hsc.wvu.edu; pithi_chan@yahoo.com
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Issue of Publication
50
ISSN
0021-9258
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Journal of Biological Chemistry
State
WV
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