Molecular roles of xCT and XB130 in esophageal squamous cell carcinoma

本研究旨在探讨半胱氨酸/谷氨酸转运体xCT在食管鳞状细胞癌（ESCC）细胞中的作用、临床意义及其与衔接蛋白XB 130的相互作用。xCT的敲低（KD）降低了ESCC细胞中XB 130的表达，并且XB 130的KD增加了xCT的表达。免疫沉淀显示xCT和XB 130之间没有相互作用。在TE 13和KYSE 170细胞中，xCT的KD抑制G1-S期进展。微阵列分析鉴定了1652个基因，其在TE 13细胞中的表达水平被xCT的KD改变。通路分析表明，G1/S检查点调控是排在第一位的通路。免疫组化染色显示xCT阳性率与Ki-67标记指数呈正相关。此外，它的表达是一个独立的预后因素。这些观察结果表明，xCT在ESCC细胞中的表达可能影响细胞周期，并影响ESCC患者的预后。

The aims of the present study were to determine the roles of xCT, cysteine/glutamate transporter in esophageal squamous cell carcinoma (ESCC) cells, its clinical significance and interaction with XB130, adaptor protein. Knocking-down (KD) of xCT decreased XB130 expression, and KD of XB130 increased xCT expression in ESCC cells. Immunoprecipitation revealed no interaction between xCT and XB130. In TE13 and KYSE170 cells, KD of xCT inhibited G1-S phase progression. Microarray analysis identified 1652 genes whose expression levels in TE13 cells were altered by the KD of xCT. Pathway analysis showed that the top-ranked pathway was the G1/S checkpoint regulation. Immunohistochemical staining showed that the xCT positivity rate was positively correlated with the Ki-67 labeling index. Further, its expression was an independent prognostic factor. These observations suggest that the expression of xCT in ESCC cells might affect the cell cycle and impact on the prognosis of ESCC patients.