The roles of Akt and NOSs in regulation of VLA-4-mediated melanoma cell adhesion to endothelial VCAM-1 after UVB-irradiation
The roles of Akt and NOSs in regulation of VLA-4-mediated melanoma cell adhesion to endothelial VCAM-1 after UVB-irradiation
复制标题
DOI：
10.1016/j.abb.2010.11.021
复制
发表时间：
2011-04-15
影响因子：
3.9
通讯作者：
Wu, Shiyong
中科院分区：
文献类型：
--
作者：
Liu, Wei;Wu, Shiyong
M624 黑色素瘤和 HUVEC 细胞之间 UVB 降低的亲合力取决于 VLA-4 与其内皮配体 VCAM-1 的相互作用。我们之前的研究表明，黑色素瘤细胞表面的 α4 整合素（VLA-4 的两个亚基之一）的空间组织导致了 UVB 照射后 VCAM-1 亲和力的变化。在这项研究中，我们证明 Akt 在 UVB 照射后调节黑色素瘤细胞上 α4 整合素的表达和表面水平方面发挥着重要作用。虽然 α4 整合素的细胞表面水平不受 UVB 照射或单独使用 Akt 抑制剂的显着影响，但当 Akt 受到抑制时，它会在 UVB 照射后动态改变。抑制 Akt 还可逆转照射后细胞亲和力的降低。我们的数据还表明 UVB 会降低 Akt 的水平。 Akt 活性的抑制与 UVB 照射后偶联的 cNOS 量和 iNOS 量的减少相关。然而，NOS 对黑色素瘤细胞粘附的影响是由于它们在 UVB 照射后调节细胞凋亡的作用而出现的。基于这些结果，我们提出 UVB 诱导的黑色素瘤细胞亲和力降低是由 NOS 和 Akt 通过两种不同机制协调调节的。由爱思唯尔公司出版
UVB-reduced avidity between M624 melanoma and HUVEC cells is dependent on the interaction of VLA-4 with its endothelial ligand VCAM-1. Our previous studies suggested that a spatial organization of alpha 4 integrin, one of the two subunits of VLA-4, on the melanoma cell surface contributed to the changes in avidity for VCAM-1 upon UVB-irradiation. In this study, we demonstrate that Akt plays an important role in regulation of the expression and surface level of alpha 4 integrin on melanoma cells upon UVB-irradiation. While the cell surface level of alpha 4 integrin is not significantly affected by UVB-irradiation or Akt inhibitor alone, it is dynamically altered after UVB-irradiation when Akt is inhibited. Inhibition of Akt also reverses the reduction of avidity of cells after the irradiation. Our data also shows that UVB reduces the level of Akt. The inhibition of Akt activity correlates with a reduced amount of coupled cNOS and reduced amount of iNOS after UVB-irradiation. However, the effect of NOSs on melanoma cell adhesion appears due to their roles in regulation of apoptosis after UVB-irradiation. Base on these results, we propose that the UVB-induced reduction of avidity of melanoma cells is coordinatively regulated by NOSs and Akt through two differential mechanisms. Published by Elsevier Inc.