Aquaporin3 is required for FGF-2-induced migration of human breast cancers.
Aquaporin3 is required for FGF-2-induced migration of human breast cancers.
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DOI：
10.1371/journal.pone.0056735
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang B
中科院分区：
文献类型：
--
作者：
Cao XC;Zhang WR;Cao WF;Liu BW;Zhang F;Zhao HM;Meng R;Zhang L;Niu RF;Hao XS;Zhang B
水通道蛋白 (AQP) 家族由许多运输水和甘油的小型整合膜蛋白组成。 AQP 对于跨上皮液体运输至关重要。最近的报告表明，AQP，特别是 AQP1 和 AQP5，在多种组织来源的高级肿瘤细胞中表达，并且 AQP 参与细胞迁移和转移。基于这一背景，我们研究了 AQP 家族的另一个重要成员 AQP3 是否可以促进人类乳腺癌的细胞迁移。使用两种代表性乳腺癌细胞系（MDA-MB-231 和 Bcap-37）检查了 AQP3 的潜在作用。简而言之，AQP3 表达被稳定表达针对 AQP3 mRNA 的 shRNA 的慢病毒构建体抑制。通过蛋白质印迹验证 AQP3 表达抑制。在成纤维细胞生长因子-2 (FGF-2) 存在的情况下，使用伤口划痕试验检查细胞迁移。在其他实验中，AQP3 被 CuSO4 抑制。成纤维细胞生长因子受体（FGFR）激酶抑制剂PD173074、PI3K抑制剂LY294002和MEK1/2抑制剂PD98059被用来剖析FGF-2诱导AQP3表达的分子机制。 FGF-2 处理以剂量依赖性方式增加 AQP3 表达并诱导细胞迁移。通过慢病毒 shRNA 沉默 AQP3 表达可抑制 FGF-2 诱导的细胞迁移。 CuSO4 是一种对 AQP3 具有选择性的水转运抑制剂，也能抑制 FGF-2 诱导的细胞迁移。 FGFR 激酶抑制剂 PD173074 显着抑制 FGF-2 诱导的 AQP3 表达和细胞迁移。 PI3K 抑制剂 LY294002 和 MEK1/2 抑制剂 PD98059 抑制但未完全阻断 FGF-2 诱导的 AQP3 表达和细胞迁移。在培养的人乳腺癌细胞中，AQP3 是 FGF-2 诱导的细胞迁移所必需的。我们的研究结果还表明 FGFR-PI3K 和 FGFR-ERK 信号在 FGF-2 诱导的 AQP3 表达中的重要性。总之，我们的研究结果表明 AQP3 在乳腺癌细胞迁移和转移中具有新功能。
The aquaporin (AQP) family consists of a number of small integral membrane proteins that transport water and glycerol. AQPs are critical for trans-epithelial fluid transport. Recent reports demonstrated that AQPs, particularly AQP1 and AQP5, are expressed in high grade tumor cells of a variety of tissue origins, and that AQPs are involved in cell migration and metastasis. Based on this background, we examined whether AQP3, another important member of the AQP family, could facilitate cell migration in human breast cancers. Potential role of AQP3 was examined using two representative breast cancer cell lines (MDA-MB-231 and Bcap-37). Briefly, AQP3 expression was inhibited with a lentivirus construct that stably expressed shRNA against the AQP3 mRNA. AQP3 expression inhibition was verified with Western blot. Cell migration was examined using a wound scratch assay in the presence of fibroblast growth factor-2 (FGF-2). In additional experiments, AQP3 was inhibited by CuSO4. Fibroblast growth factor receptor (FGFR) kinase inhibitor PD173074, PI3K inhibitor LY294002, and MEK1/2 inhibitor PD98059 were used to dissect the molecular mechanism of FGF-2 induced AQP3 expression. FGF-2 treatment increased AQP3 expression and induced cell migration in a dose dependent manner. Silencing AQP3 expression by a lentiviral shRNA inhibited FGF-2 induced cell migration. CuSO4, a water transport inhibitor selective for AQP3, also suppressed FGF-2-induced cell migration. The FGFR kinase inhibitor PD173074, significantly inhibited FGF-2-induced AQP3 expression and cell migration. The PI3K inhibitor LY294002 and MEK1/2 inhibitor PD98059 inhibited, but not fully blocked, FGF-2-induced AQP3 expression and cell migration. AQP3 is required for FGF-2-induced cell migration in cultured human breast cancer cells. Our findings also suggest the importance of FGFR-PI3K and FGFR-ERK signaling in FGF-2-induced AQP3 expression. In summary, our findings suggest a novel function of AQP3 in cell migration and metastasis of breast cancers.
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DOI：
10.1016/s0006-291x(02)00350-9
发表时间：
2002-05-17
影响因子：
3.1
作者：
Liu, JF;Crépin, M;Ledoux, D
通讯作者：
Ledoux, D
影响因子：
8
作者：
Moon, C;Soria, JC;Mao, L
通讯作者：
Mao, L
影响因子：
2.7
作者：
Li, HP;Kamiie, J;Yamamoto, T
通讯作者：
Yamamoto, T
影响因子：
3.8
作者：
Otterbach, Friedrich;Callies, Rainer;Bankfalvi, Agnes
通讯作者：
Bankfalvi, Agnes
影响因子：
4
作者：
Vicente-Manzanares, M;Webb, DJ;Horwitz, AR
通讯作者：
Horwitz, AR