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水通道蛋白9通过AKT信号通路促进星形细胞瘤细胞的侵袭和迁移。

AQP9 promotes astrocytoma cell invasion and motility via the AKT pathway.

作者信息

Lv Yao, Huang Qiang, Dai Weimin, Jie Yuanqing, Yu Guofeng, Fan Xiaofeng, Wu An, Miao Qian

机构信息

Department of Neurosurgery, Quzhou People's Hospital, Quzhou, Zhejiang 324000, P.R. China.

Department of Oncology, Quzhou People's Hospital, Quzhou, Zhejiang 324000, P.R. China.

出版信息

Oncol Lett. 2018 Nov;16(5):6059-6064. doi: 10.3892/ol.2018.9361. Epub 2018 Aug 23.

DOI:10.3892/ol.2018.9361
PMID:30344749
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6176364/
Abstract

The aquaporin (AQP) family, which includes 13 members identified in mammalian cells, is involved in cancer development and progression. AQP9 expression is upregulated in several tumor tissue types. However, the functions of AQP9 in astrocytoma remain elusive. The present study identified that AQP9 was expressed in astrocytoma cells. AQP9 expression was silenced by transfection with small interfering RNAs and increased by transfection with a plasmid containing the AQP9 gene. Using invasion and wound-healing assays, it was revealed that the knockdown of AQP9 suppressed astrocytoma cell invasion and motility, whereas overexpression of AQP9 promoted the invasion and motility of astrocytoma cells. It was further revealed that AQP9 could induce RAC serine/threonine-protein kinase (AKT) activation and decrease E-cadherin expression in astrocytoma cells. Inhibition of the AKT pathway attenuated AQP9-mediated invasion, motility and E-cadherin expression. Taken together, the results of the present study indicated that AQP9 promoted the invasion and motility of cells via the AKT pathway. Therefore, AQP9 may represent a potential target for therapeutic use of astrocytoma.

摘要

水通道蛋白(AQP)家族包括在哺乳动物细胞中鉴定出的13个成员,参与癌症的发生和发展。AQP9在几种肿瘤组织类型中表达上调。然而,AQP9在星形细胞瘤中的功能仍不清楚。本研究发现AQP9在星形细胞瘤细胞中表达。通过转染小干扰RNA使AQP9表达沉默,通过转染含AQP9基因的质粒使AQP9表达增加。使用侵袭和伤口愈合试验,发现敲低AQP9可抑制星形细胞瘤细胞的侵袭和运动能力,而AQP9的过表达则促进星形细胞瘤细胞的侵袭和运动能力。进一步发现,AQP9可诱导星形细胞瘤细胞中RAC丝氨酸/苏氨酸蛋白激酶(AKT)激活并降低E-钙黏蛋白表达。抑制AKT途径可减弱AQP9介导的侵袭、运动能力和E-钙黏蛋白表达。综上所述,本研究结果表明,AQP9通过AKT途径促进细胞的侵袭和运动能力。因此,AQP9可能是星形细胞瘤治疗的潜在靶点。

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本文引用的文献

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Down-regulation of AQP4 Inhibits Proliferation, Migration and Invasion of Human Breast Cancer Cells.水通道蛋白4的下调抑制人乳腺癌细胞的增殖、迁移和侵袭。
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Aquaporin 9 inhibits hepatocellular carcinoma through up-regulating FOXO1 expression.水通道蛋白9通过上调FOXO1表达抑制肝细胞癌。
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Aquaporin 9 is down-regulated in hepatocellular carcinoma and its over-expression suppresses hepatoma cell invasion through inhibiting epithelial-to-mesenchymal transition.水通道蛋白9在肝细胞癌中表达下调,其过表达通过抑制上皮-间质转化来抑制肝癌细胞侵袭。
Cancer Lett. 2016 Aug 10;378(2):111-9. doi: 10.1016/j.canlet.2016.05.021. Epub 2016 May 20.
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Effect of AQP9 Expression in Androgen-Independent Prostate Cancer Cell PC3.水通道蛋白9(AQP9)表达在雄激素非依赖性前列腺癌细胞PC3中的作用。
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Aquaporin 3 promotes prostate cancer cell motility and invasion via extracellular signal-regulated kinase 1/2-mediated matrix metalloproteinase-3 secretion.水通道蛋白3通过细胞外信号调节激酶1/2介导的基质金属蛋白酶-3分泌促进前列腺癌细胞的迁移和侵袭。
Mol Med Rep. 2015 Apr;11(4):2882-8. doi: 10.3892/mmr.2014.3097. Epub 2014 Dec 16.
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Transcription regulation of E-cadherin by zinc finger E-box binding homeobox proteins in solid tumors.实体瘤中锌指E盒结合同源框蛋白对E-钙黏蛋白的转录调控
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