Anion exchanger 2 suppresses cellular movement and has prognostic significance in esophageal squamous cell carcinoma.
Anion exchanger 2 suppresses cellular movement and has prognostic significance in esophageal squamous cell carcinoma.
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阴离子交换器2抑制细胞运动，并在食管鳞状细胞癌中具有预后意义。
DOI：
10.18632/oncotarget.25417
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发表时间：
2018-05-25
期刊：
影响因子：
--
通讯作者：
Otsuji E
中科院分区：
文献类型：
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作者：
Shiozaki A;Hikami S;Ichikawa D;Kosuga T;Shimizu H;Kudou M;Yamazato Y;Kobayashi T;Shoda K;Arita T;Konishi H;Komatsu S;Kubota T;Fujiwara H;Okamoto K;Kishimoto M;Konishi E;Marunaka Y;Otsuji E
最近的研究报道了各种细胞内pH调节剂在上皮癌发生和肿瘤进展中的重要作用。本研究旨在探讨阴离子交换蛋白2（AE2）在食管鳞状细胞癌（ESCC）中对肿瘤进展相关基因的调控作用及其表达的预后价值。AE2在KYSE 170和TE 13细胞中呈强表达。AE2在这些细胞中的耗竭增加了细胞迁移并抑制了细胞凋亡的诱导。微阵列分析的结果显示，各种基质金属蛋白酶（MMP）信号通路相关的基因，如MMP 1，MMP 12和TIMP 4，在AE2缺失的KYSE 170细胞中上调或下调。免疫组化染色显示，AE2主要定位于癌细胞的细胞膜或胞浆，其在肿瘤浸润前沿的表达模式与pT类型有关。预后分析显示，AE2在浸润前沿的低级别表达与较短的术后生存期相关。本研究的结果表明，ESCC中AE2的减少通过激活MMP信号通路增强细胞运动，并与ESCC患者的不良预后相关。在人ESCC细胞系中，使用AE2 siRNA进行敲低实验，并分析对细胞运动和存活的影响。使用微阵列分析检测细胞的基因表达谱。对61例食管鳞癌患者行食管切除术后的原发肿瘤标本进行免疫组化分析。
Recent studies have reported essential roles for various intracellular pH regulators in epithelial carcinogenesis and tumor progression. The aims of the present study were to investigate the role of anion exchanger 2 (AE2) in the regulation of tumor progression-related genes and the prognostic value of its expression in esophageal squamous cell carcinoma (ESCC). AE2 was strongly expressed in KYSE170 and TE13 cells. The depletion of AE2 in these cells increased cell migration and inhibited the induction of apoptosis. The results of the microarray analysis revealed that various matrix metalloproteinase (MMP) signaling pathway-related genes, such as MMP1, MMP12, and TIMP4, were up- or down-regulated in AE2-depleted KYSE170 cells. Immunohistochemical staining showed that AE2 was primarily located in the cell membranes or cytoplasm of carcinoma cells, and its expression pattern at the invasive front of the tumor was related to the pT category. Prognostic analyses revealed that the low-grade expression of AE2 at the invasive front was associated with shorter postoperative survival. The results of the present study suggest that reductions in AE2 in ESCC enhance cellular movement by activating MMP signaling pathways and are related to a poor prognosis in patients with ESCC. In human ESCC cell lines, knockdown experiments were conducted using AE2 siRNA, and the effects on cellular movement and survival were analyzed. The gene expression profiles of cells were examined using a microarray analysis. An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy.