Tuberin-deficiency downregulates N-cadherin and upregulates vimentin in kidney tumor of TSC patients.
Tuberin-deficiency downregulates N-cadherin and upregulates vimentin in kidney tumor of TSC patients.
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DOI：
10.18632/oncotarget.2206
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发表时间：
2014-08-30
期刊：
影响因子：
--
通讯作者：
Habib SL
中科院分区：
文献类型：
--
作者：
Liang S;Salas T;Gencaslan E;Li B;Habib SL
血管肌脂肪瘤(AML)与结节性硬化症患者肾脏的细胞纤维化有关。纤维蛋白在急性淋巴细胞性白血病中积聚的机制尚不清楚。在本研究中，我们研究了Akt/tuberin/mTOR通路在调节细胞纤维化蛋白中的作用。与HEK293细胞相比，表达低水平tuberin的AML细胞N-钙粘蛋白表达较少，而波形蛋白表达较高。AML细胞感染Ad-tuberin后，波形蛋白表达明显减少，N-钙粘附素蛋白表达增加。此外，经雷帕霉素处理的细胞p-Akt显著增加，p-p70S6K减少，这与波形蛋白表达减少和N-钙粘蛋白表达略有增加有关。另一方面，Akt抑制剂处理的细胞显示p-Akt和p-p70S6K的表达显著减少，这与波形蛋白的显著减少和N-钙粘蛋白的表达增加有关。此外，转染dN-Akt或dN-S6K的细胞N-钙粘蛋白表达显著增加，而波形蛋白表达明显减少。此外，转染抗Rictor的siRNA或抗Raptor的siRNA的细胞，波形蛋白表达减少，N-钙粘蛋白的表达增加。与对照肾组织相比，TSC患者肾肿瘤组织中N-钙粘附素的表达显著降低，Vimentin蛋白的表达显著增加。这些数据构成了第一份报告，提供了Akt/tuberin/mTORC1/2在调节N-钙粘素和波形蛋白中的作用，这两种蛋白参与了TSC患者肾脏肿瘤纤维化的进展。
Angiomyolipomas (AMLs) are associated with cell fibrosis in kidney of Tuberous Sclerosis Complex patients. The mechanism by which the fibrotic proteins accumulated in AMLs has not been explored. In the present study, we investigated the role of Akt/tuberin/mTOR pathway in the regulation cell fibrosis proteins. AML cells that expressed low levels of tuberin showed less expression of N-cadherin and higher of vimentin proteins compared to HEK293 cells. AML cells infected with Ad-tuberin showed a significant decrease in vimentin and an increase in N-cadherin protein expression. In addition, cells treated with rapamycin showed a significant increase in p-Akt and a decrease in p-p70S6K that was associated with a decrease expression of vimentin and a slight increase expression in N-cadherin. On the other hand, cells treated with Akt inhibitor revealed a significant decrease in p-Akt and p-p70S6K that was associated with a significant decrease in vimentin and an increase in N-cadherin expression. In addition, cells transfected with DN-Akt or DN-S6K show significant increase expression in N-cadherin and a decrease in vimentin. Moreover, cells transfected with siRNA against rictor or siRNA against raptor resulted in a decrease in vimentin and an increase N-cadherin expression. Kidney tumors from TSC patients showed significant decrease in N-cadherin and significant increased in vimentin protein expression compared to control kidney tissues. These data comprise the first report to provide the role of Akt/tuberin/mTORC1/2 in the regulation of N-cadherin and vimentin that are involved in the progression of fibrosis in kidney tumor of TSC patients.
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