The down-regulation of TAPP2 inhibits the migration of esophageal squamous cell carcinoma and predicts favorable outcome
The down-regulation of TAPP2 inhibits the migration of esophageal squamous cell carcinoma and predicts favorable outcome
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TAPP2的下调抑制食管鳞状细胞癌的迁移并预测良好的结果
DOI：
10.1016/j.prp.2017.09.010
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Songhua Lu
中科院分区：
文献类型：
--
作者：
Fang Liu;Fei Ye;Zongyu Guan;Yi Zhou;Fengjun Ji;Qing Zhang;Jianping Zhang;Tianyi Zhang;Songhua Lu
含有串联pH结构域的蛋白质TAPP 1和TAPP 2是特异性结合磷脂酰肌醇-3，4-二磷酸或PI（3，4）P2（磷酸肌醇3-激酶（PI 3 K）的产物）的衔接蛋白。尽管PI 3 K酶在细胞生物学中具有多种功能，包括细胞迁移，但PI（3，4）P2及其结合蛋白的功能还不清楚。先前的研究发现TAPP 2在具有强迁移能力的原代白血病B细胞中高度表达。然而，TAPP 2在ESCC中的功能和潜在机制仍不清楚。在本研究中，我们通过免疫组织化学（IHC）和蛋白质印迹分析研究了TAPP 2在人食管鳞状细胞癌（ESCC）组织和相应的癌旁非肿瘤组织中的水平。TAPP 2蛋白在食管鳞癌组织中的表达明显高于癌旁组织。体外实验结果表明，TAPP 2的低表达降低了ESCC细胞TE 1的迁移能力，并伴随着AKT磷酸化水平的降低。综上所述，这些发现表明TAPP 2在ESCC中作为致癌基因，并可能作为ESCC治疗的新靶点。
Tandem pH domain-containing proteins TAPP1 and TAPP2 are adaptor proteins that specifically bind to.phosphatidylinositol-3,4-bisphosphate, or PI(3,4)P2, a product of phosphoinositide 3-kinases (PI3K). Although.PI3K enzymes have multiple functions in cell biology, including cell migration, the functions of PI (3, 4) P2 and.its binding proteins are not well understood. Previously studies found that TAPP2 is highly expressed in primary.leukemic B cells that have strong migratory capacity. However, the function and underlying mechanisms of.TAPP2 in ESCC remain largely unknown. In the present study, we investigated the level of TAPP2 in human.esophageal squamous cell carcinoma (ESCC) tissues and in corresponding adjacent non-tumor tissues by immunohistochemistry (IHC) and western blot analyses. TAPP2 protein level was increased in ESCC tissues.compared with corresponding adjacent non-tumor tissues. In vitro experiments showed that under-expression of.TAPP2 reduced ESCC cell TE1 migration by wound-healing assays and transwell migration assays, and it was.concurrent with the decreased expression of the phosphorylation of AKT. Taken together, these findings suggested that TAPP2 serves as oncogenic gene in ESCC and may serve as a new target for ESCC therapy.