期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 361, 期 1-2, 页码 235-241出版社
SPRINGER
DOI: 10.1007/s11010-011-1108-7
关键词
FAK; HIF-1 alpha; Integrins; Prolidase; Thrombin; Colon adenocarcinoma
类别
Products of prolidase [E.C. 3.4.13.9] activity, proline or hydroxyproline, contribute to up-regulation of hypoxia-inducible factor-1 alpha (HIF-1 alpha). Prolidase activity is regulated by beta(1)-integrin signaling. We studied the effects of echistatin (a well-known disintegrin) and thrombin (a serine protease capable of activation of integrin alpha(2)beta(1) receptor) on prolidase activity and expressions of prolidase, alpha(2)beta(1)-integrin receptor, focal adhesion kinase (FAK), MAP-kinases (ERK1 and ERK2), and nuclear HIF-1 alpha in human colon adenocarcinoma (DLD-1) cells. It has been found that treatment of the cells with thrombin contributes to decrease in the expression of prolidase and simultaneously increase in its phosphorylation, resulting in maintenance of the enzyme activity. The phenomenon was accompanied by thrombin-dependent recovery of depressed autophosphorylation of FAK (pY(397)) under the effect of FAK inhibitor (1,2,4,5-benzenetetramine tetrahydrochloride). Although integrin alpha(2)beta(1) receptor expression was not affected by thrombin, the signaling induced by thrombin up-regulated nuclear HIF-1 alpha expression. It was accompanied by increase in the expression of MAP kinases, ERK1 and ERK2. It suggests that integrin-dependent signaling through p-FAK is up-regulated in DLD-1 cells and it may represent potential target for anti-cancer therapy.
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