Gankyrin is essential for hypoxia enhanced metastatic potential in breast cancer cells
Gankyrin is essential for hypoxia enhanced metastatic potential in breast cancer cells
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DOI：
10.3892/mmr.2013.1860
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发表时间：
2014-03-01
影响因子：
3.4
通讯作者：
Song, Haifeng
中科院分区：
文献类型：
--
作者：
Gao, Liucun;Xie, Huahong;Song, Haifeng
缺氧是肿瘤生长和转移的重要调节因子，可诱导增殖、迁移和侵袭等多种途径的转录激活。Gankyrin在乳腺癌细胞中被发现过表达，也促进了乳腺癌细胞的转移，这也参与了缺氧诱导因子-1和缺氧诱导因子-1的调控。本研究发现，低氧条件下BT474乳腺癌细胞系中gankyrin mRNA和蛋白表达增加，细胞迁移和侵袭能力增强。将慢病毒介导的靶向gankyrin的siRNA转染到BT474细胞中。伤口愈合和transwell实验表明，gankyrin缺失消除了BT474细胞因缺氧而增加的迁移和侵袭。此外，我们还发现E-cadherin参与了gankyrin诱导的乳腺癌细胞缺氧侵袭。本研究表明，缺失gankyrin部分通过调节E-cadherin消除了缺氧条件下乳腺癌细胞增加的转移潜能，提示对gankyrin的进一步了解可能为治疗人类乳腺癌转移提供潜在的治疗靶点。
Hypoxia, a critical regulator of tumor growth and metastasis, induces the transcriptional activation of several pathways involved in proliferation, migration and invasion. Gankyrin was found to be overexpressed, and also promoted the metastasis in breast cancer cells, which is also involved in the regulation of hypoxia inducible factor-1 and hypoxia-inducible factor-1. The present study showed that gankyrin mRNA and protein expression were increased under hypoxic conditions in the BT474 breast cancer cell line, accompanied with increased ability of cell migration and invasion. Lentivirus-mediated siRNA targeting gankyrin was transfected into BT474 cells. Wound-healing and transwell experiments showed that gankyrin deletion abrogated the increased migration and invasion of BT474 cells due to hypoxia. In addition, E-cadherin was found to be involved in the gankyrin induced invasion of breast cancer cells due to hypoxia. The present study indicated that gankyrin deletion abrogated the increased metastatic potential of breast cancer cells under hypoxic conditions partly through regulating E-cadherin, suggesting that an improved understanding of gankyrin may offer a potential therapeutic target for the treatment of human breast cancer metastasis.