Acquisition of epithelial-mesenchymal transition is associated with Skp2 expression in paclitaxel-resistant breast cancer cells.

Acquisition of epithelial-mesenchymal transition is associated with Skp2 expression in paclitaxel-resistant breast cancer cells.
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DOI:
10.1038/bjc.2014.136
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发表时间:
2014-04-15
影响因子:
8.8
通讯作者:
Wang, Z.
Wang, Z.
中科院分区:
医学1区
文献类型:
--
作者:
Yang, Q.;Huang, J.;Wu, Q.;Cai, Y.;Zhu, L.;Lu, X.;Chen, S.;Chen, C.;Wang, Z.

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乳腺癌是最常见的女性恶性疾病,也是美国癌症相关死亡的第二大原因。获得性耐药是导致乳腺癌治疗效果差的重要原因。因此,阐明乳腺癌耐药机制是当务之急。为了研究乳腺癌中获得性紫杉醇耐药细胞的潜在分子基础,我们使用了多种方法,包括实时RT-PCR,Western印迹分析,迁移和侵袭试验,伤口愈合试验和转染。我们发现,上皮间质转化(EMT)参与紫杉醇耐药(PR)乳腺癌细胞。具有EMT特征的耐药细胞表现出更强的迁移和侵袭活性。在机制上,发现Skp 2的高表达与PR细胞中的EMT相关。值得注意的是,PR细胞中Skp 2的缺失导致EMT表型的部分逆转。这些发现表明Skp 2在PR介导的EMT中起重要作用。Skp 2可能成为乳腺癌潜在的治疗靶点。
Breast cancer is the most common female malignant disease, and the second leading cause of cancer-related death in the United States. Acquired resistance to chemotherapeutic drugs is a pivotal reason that leads to worse treatment outcome of breast cancer. Therefore, it is urgent to elucidate the mechanism of drug resistance in breast cancer. To investigate the underlying molecular basis of the acquired resistant cells to paclitaxel in breast cancer, we used multiple methods including real-time RT–PCR, western blotting analysis, migration and invasion assays, wound healing assay, and transfection. We found that epithelial–mesenchymal transition (EMT) is involved in paclitaxel-resistant (PR) breast cancer cells. The resistant cells with EMT features exhibit increased migration and invasion activities. Mechanistically, high expression of Skp2 was found to be associated with EMT in PR cells. Notably, depletion of Skp2 in PR cells led to partial reversal of EMT phenotype. These findings suggest that Skp2 was critically involved in PR-mediated EMT. Skp2 could be a potential therapeutic target for breast cancer.
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