Thymosin beta 4 regulates migration of colon cancer cells by a pathway involving interaction with Ku80

Aberrant expression of thymosin beta 4 (T beta 4) has recently been found to be associated with colorectal carcinoma (CRC) progression evidently due to an increase of the motility and invasion of tumor cells and the induction of a proangiogenic phenotype of endothelial cells. Both mechanisms depend...

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Bibliographic Details
Published in:Annals of the New York Academy of Sciences 2010-04, Vol.1194 (1), p.60-71
Main Authors: Cierniewski, Czeslaw S, Papiewska-Pajak, Izabela, Malinowski, Mariusz, Sacewicz-Hofman, Izabela, Wiktorska, Magdalena, Kryczka, Jakub, Wysocki, Tomasz, Niewiarowska, Jolanta, Bednarek, Radoslaw
Format: Article
Language:English
Subjects:
Biological
Colon
Endothelial cells
Fibrin
Gels
Macromolecules
Matrix metalloproteinases
Three dimensional
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Summary:Aberrant expression of thymosin beta 4 (T beta 4) has recently been found to be associated with colorectal carcinoma (CRC) progression evidently due to an increase of the motility and invasion of tumor cells and the induction of a proangiogenic phenotype of endothelial cells. Both mechanisms depend upon matrix-degrading proteases, particularly plasmin and matrix metalloproteinases (MMPs) that are responsible for extensive tissue remodeling. Cleavage of ECM macromolecules weakens the structural integrity of tissues and exposes cryptic domains of extracellular components, which elicit biological responses distinct from intact molecules. Interestingly, signaling via integrins ( alpha V beta 3, alpha 5 beta 1) in CRC cells (HT29, CX1.1) is induced by T beta 4 and VEGF-A only when they grow in 3D fibrin gels but not in 2D ones. The cells growing in 3D fibrin gels release upon T beta 4 significant amounts of active MMPs (MMP-2, MMP-9, and MMP-7) that cause extensive proteolysis in their close vicinity. As evidenced by a variety of approaches (transfection experiments, coimmunoprecipitation, gene silencing with siRNA), we found that this involves interaction of T beta 4 with Ku80, which has recently been described by us to mediate T beta 4 intracellular activity.
ISSN:0077-8923
DOI:10.1111/j.1749-6632.2010.05480.x