CDK5 is essential for TGF-β1-induced epithelial-mesenchymal transition and breast cancer progression.
CDK5 is essential for TGF-β1-induced epithelial-mesenchymal transition and breast cancer progression.
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DOI：
10.1038/srep02932
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发表时间：
2013-10-14
影响因子：
4.6
通讯作者：
Lu, Jun
中科院分区：
文献类型：
--
作者：
Liang, Qian;Li, Lili;Zhang, Jianchao;Lei, Yang;Wang, Liping;Liu, Dong-Xu;Feng, Jingxin;Hou, Pingfu;Yao, Ruosi;Zhang, Yu;Huang, Baiqu;Lu, Jun
上皮-间质转化是细胞可塑性的改变，对胚胎发育和肿瘤转移至关重要。CDK 5是一种脯氨酸导向的丝氨酸/苏氨酸激酶，在癌症进展中发挥重要作用。在这里，我们发现CDK 5通常过表达，并与乳腺癌的几个不良预后参数显着相关。我们发现CDK 5参与了TGF-β1诱导的EMT。在MCF 10A中，TGF-β1上调CDK 5和p35的表达，而CDK 5敲低抑制TGF-β1诱导的EMT。CDK 5过表达在促进TGF-β1诱导的EMT中也表现出潜在的协同作用。在间充质乳腺癌细胞MDA-MB-231和BT549中，CDK 5敲低抑制细胞运动和肿瘤发生。我们进一步证明CDK 5通过调节FAK在Ser-732的磷酸化来调节癌细胞迁移和肿瘤形成。因此，CDK 5-FAK通路作为TGF-β1信号转导的下游环节，对乳腺癌细胞的EMT和运动性至关重要。本研究暗示了CDK 5作为乳腺癌分子标志物的潜在价值。
Epithelial-mesenchymal transition is a change of cellular plasticity critical for embryonic development and tumor metastasis. CDK5 is a proline-directed serine/threonine kinase playing important roles in cancer progression. Here we show that CDK5 is commonly overexpressed and significantly correlated with several poor prognostic parameters of breast cancer. We found that CDK5 participated in TGF-β1-induced EMT. In MCF10A, TGF-β1 upregulated the CDK5 and p35 expression, and CDK5 knockdown inhibited TGF-β1-induced EMT. CDK5 overexpression also exhibited a potential synergy in promoting TGF-β1-induced EMT. In mesenchymal breast cancer cells MDA-MB-231 and BT549, CDK5 knockdown suppressed cell motility and tumorigenesis. We further demonstrated that CDK5 modulated cancer cell migration and tumor formation by regulating the phosphorylation of FAK at Ser-732. Therefore, CDK5-FAK pathway, as a downstream step of TGF-β1 signaling, is essential for EMT and motility in breast cancer cells. This study implicates the potential value of CDK5 as a molecular marker for breast cancer.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
11.2
作者：
Feldmann G;Mishra A;Hong SM;Bisht S;Strock CJ;Ball DW;Goggins M;Maitra A;Nelkin BD
通讯作者：
Nelkin BD
影响因子：
25
作者：
Hawasli, Ammar H.;Benavides, David R.;Bibb, James A.
通讯作者：
Bibb, James A.
DOI：
10.1073/pnas.0712306105
发表时间：
2008-05-27
影响因子：
11.1
作者：
Liu, Ren;Tian, Bo;Mao, Zixu
通讯作者：
Mao, Zixu