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首页> 外文期刊>Molecular and Cellular Biology >Aquaporin-3 Controls Breast Cancer Cell Migration by Regulating Hydrogen Peroxide Transport and Its Downstream Cell Signaling
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Aquaporin-3 Controls Breast Cancer Cell Migration by Regulating Hydrogen Peroxide Transport and Its Downstream Cell Signaling

机译：Aquaporin-3通过调节过氧化氢转运及其下游细胞信号传导来控制乳腺癌细胞的迁移。

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Most breast cancer mortality is due to clinical relapse associated with metastasis. CXCL12/CXCR4-dependent cell migration is a critical process in breast cancer progression; however, its underlying mechanism remains to be elucidated. Here, we show that the water/glycerol channel protein aquaporin-3 (AQP3) is required for CXCL12/CXCR4-dependent breast cancer cell migration through a mechanism involving its hydrogen peroxide (H2O2) transport function. Extracellular H2O2, produced by CXCL12-activated membrane NADPH oxidase 2 (Nox2), was transported into breast cancer cells via AQP3. Transient H2O2 accumulation was observed around the membrane during CXCL12-induced migration, which may be facilitated by the association of AQP3 with Nox2. Intracellular H2O2 then oxidized PTEN and protein tyrosine phosphatase 1B (PTP1B) followed by activation of the Akt pathway. This contributed to directional cell migration. The expression level of AQP3 in breast cancer cells was related to their migration ability both in vitro and in vivo through CXCL12/CXCR4- or H2O2-dependent pathways. Coincidentally, spontaneous metastasis of orthotopic xenografts to the lung was reduced upon AQP3 knockdown. These findings underscore the importance of AQP3-transported H2O2 in CXCL12/CXCR4-dependent signaling and migration in breast cancer cells and suggest that AQP3 has potential as a therapeutic target for breast cancer.
机译：大多数乳腺癌死亡率是由于与转移相关的临床复发所致。 CXCL12 / CXCR4依赖性细胞迁移是乳腺癌进展的关键过程。但是，其潜在机制尚待阐明。在这里，我们表明水/甘油通道蛋白aquaporin-3（AQP3）是CXCL12 / CXCR4依赖性乳腺癌细胞通过其过氧化氢（H 2 O 2 ）传输功能。 CXCL12激活的膜NADPH氧化酶2（Nox2）产生的细胞外H 2 O 2 通过AQP3转运到乳腺癌细胞中。在CXCL12诱导的迁移过程中，在膜周围观察到瞬时H 2 O 2 积累，这可能是由于AQP3与Nox2的缔合所致。细胞内H 2 O 2 然后氧化PTEN和蛋白酪氨酸磷酸酶1B（PTP1B），然后激活Akt途径。这有助于定向细胞迁移。乳腺癌细胞中AQP3的表达水平与其在体外 和体内通过CXCL12 / CXCR4-或H 2 的迁移能力有关。 O 2 依赖性途径。巧合的是，在敲低AQP3后，原位异种移植到肺的自发转移减少了。这些发现强调了AQP3转运的H 2 O 2 在乳腺癌细胞中依赖CXCL12 / CXCR4的信号传导和迁移中的重要性，并表明AQP3具有潜在的治疗靶点乳腺癌。

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