Cdk3-promoted epithelial-mesenchymal transition through activating AP-1 is involved in colorectal cancer metastasis.
Cdk3-promoted epithelial-mesenchymal transition through activating AP-1 is involved in colorectal cancer metastasis.
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Cdk3通过激活AP-1促进上皮间质转化参与结直肠癌转移
DOI：
10.18632/oncotarget.6875
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发表时间：
2016-02-09
期刊：
影响因子：
--
通讯作者：
Tang F
中科院分区：
文献类型：
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作者：
Lu J;Zhang ZL;Huang D;Tang N;Li Y;Peng Z;Lu C;Dong Z;Tang F
细胞周期蛋白依赖性激酶3（Cdk 3）是哺乳动物细胞周期G1期的正调控因子。cdk 3参与了癌症的进展，但对其在癌症发生和发展中的机制知之甚少。在此，我们发现Cdk 3通过促进上皮-间质转化（EMT）移位增加结直肠癌转移。cdk 3在转移癌中高表达，并诱导细胞运动和侵袭。Cdk 3显示在体外和离体中在Ser 63和Ser 73处磷酸化c-Jun。Cdk 3-磷酸化的c-Jun在Ser 63和Ser 73导致AP-1活性增加。Cdk 3的异位表达促进结直肠癌从上皮向间充质转化结合AP-1激活，而AP-1抑制显着降低Cdk 3增加EMT移位。这些结果表明，Cdk 3/c-Jun信号轴介导的上皮-间质转化在结直肠癌转移中起重要作用。
Cyclin dependent kinase-3 (Cdk3) is a positive regulator of the G1 mammalian cell cycle phase. Cdk3 is involved in cancer progression, but very little is known about its mechanism in cancer development and progression. Herein, we found that Cdk3 increased colorectal cancer metastasis through promoting epithelial-mesenchymal transition (EMT) shift. Cdk3 was found to highly express in metastatic cancer and induce cell motility and invasion. Cdk3 was shown to phosphorylate c-Jun at Ser 63 and Ser 73 in vitro and ex vivo. Cdk3-phosphorylated c-Jun at Ser 63 and Ser 73 resulted in an increased AP-1 activity. Ectopic expression of Cdk3 promoted colorectal cancer from epithelial to mesenchymal transition conjugating AP-1 activation, while AP-1 inhibition dramatically decreased Cdk3-increased EMT shift. These results showed that the Cdk3/c-Jun signaling axis mediating epithelial-mesenchymal transition plays an important role in colorectal cancer metastasis.