Oncotarget

Research Papers:

Cdk3-promoted epithelial-mesenchymal transition through activating AP-1 is involved in colorectal cancer metastasis

Jinping Lu, Zhen Lin Zhang, Damao Huang, Na Tang, Yuejin Li, Zhengke Peng, Chengrong Lu, Zigang Dong and Faqing Tang _

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Oncotarget. 2016; 7:7012-7028. https://doi.org/10.18632/oncotarget.6875

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Abstract

Jinping Lu1,*, Zhen Lin Zhang1,*, Damao Huang2,*, Na Tang3, Yuejin Li1, Zhengke Peng1, Chengrong Lu3, Zigang Dong4 and Faqing Tang1,2

1 Clinical Laboratory and Medical Research Center, Zhuhai Hospital of Jinan University, Zhuhai People’s Hospital, Zhuhai, P.R. China

2 Clinical Laboratory, Xiangya Hospital of Central South University, Changsha, P.R. China

3 Institution of Pathogenic Biology, Medical College, University of South China, Hengyang, P.R. China

4 Hormel Institute, University of Minnesota, Austin, Minnesota, USA

* These authors have contributed equally to this work

Correspondence to:

Faqing Tang, email:

Keywords: Cdk3, colorectal cancer, AP-1, epithelial-mesenchymal transition, metastasis

Received: August 16, 2015 Accepted: January 04, 2016 Published: January 09, 2016

Abstract

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.


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