Department of Chemistry and Biochemistry, Edison Biotechnology Institute and Molecular and Cellular Biology Program, Ohio University, Athens, OH 45701, USA.
Arch Biochem Biophys. 2011 Apr 15;508(2):192-7. doi: 10.1016/j.abb.2010.11.021. Epub 2010 Dec 1.
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 α4 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 α4 integrin on melanoma cells upon UVB-irradiation. While the cell surface level of α4 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.
UVB 降低 M624 黑色素瘤细胞与 HUVEC 细胞之间的亲和性取决于 VLA-4 与其内皮配体 VCAM-1 的相互作用。我们之前的研究表明，α4 整合素（VLA-4 的两个亚基之一）在黑色素瘤细胞表面的空间组织有助于紫外线照射后 VCAM-1 亲和力的变化。在这项研究中，我们证明 Akt 在紫外线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重要作用。虽然紫外线照射或 Akt 抑制剂单独作用对α4 整合素的细胞表面水平没有显著影响，但在 Akt 被抑制后，紫外线照射后其水平会发生动态变化。Akt 的抑制也会逆转照射后细胞亲和性的降低。我们的数据还表明，紫外线会降低 Akt 的水平。Akt 活性的抑制与紫外线照射后偶联的 cNOS 和 iNOS 的量减少相关。然而，NOSs 对黑色素瘤细胞黏附的影响似乎是由于它们在紫外线照射后调节细胞凋亡的作用。基于这些结果，我们提出，紫外线诱导的黑色素瘤细胞亲和性降低是由 NOSs 和 Akt 通过两种不同的机制协调调节的。
