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, Faqing Tang

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7012-7028
Number of pages17
JournalOncotarget
Volume7
Issue number6
DOIs
StatePublished - 2016

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China (81372282, 81000881, 81402368, 81402265 and 81502346), Zhuhai Best Medical Instrument Appliance Inc., and the Foundation of State Key Laboratory of Oncology in South China (HN2011-04).

Keywords

  • AP-1
  • Cdk3
  • Colorectal cancer
  • Metastasis
  • epithelial-mesenchymal transition

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