Cyclin-dependent kinase 2 (CDK2) is a key mediator for EGF-induced cell transformation mediated through the ELK4/c-Fos signaling pathway

C. Peng, W. Zeng, J. Su, Y. Kuang, Y. He, S. Zhao, J. Zhang, Wei-Ya Ma, A. M. Bode, Zigang Dong, X. Chen

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Cyclin-dependent kinase 2 (CDK2) is a known regulator in the cell cycle control of the G1/S and S/G2 transitions. However, the role of CDK2 in tumorigenesis is controversial. Evidence from knockout mice as well as colon cancer cell lines indicated that CDK2 is dispensable for cell proliferation. In this study, we found that ectopic CDK2 enhances Ras (G12V)-induced foci formation and knocking down CDK2 expression markedly decreases epidermal growth factor (EGF)-induced cell transformation mediated through the downregulation of c-fos expression. Interestingly, CDK2 directly phosphorylates ELK4 at Thr194 and Ser387 and regulates the ELK4 transcriptional activity, which serves as a mechanism to regulate c-fos expression. In addition, ELK4 is overexpressed in melanoma and knocking down the ELK4 or CDK2 expression significantly attenuated the malignant phenotype of melanoma cells. Taken together, our study reveals a novel function of CDK2 in EGF-induced cell transformation and the associated signal transduction pathways. This indicates that CDK2 is a useful molecular target for the chemoprevention and therapy against skin cancer.

Original languageEnglish (US)
Pages (from-to)1170-1179
Number of pages10
JournalOncogene
Volume35
Issue number9
DOIs
StatePublished - Mar 3 2016

Bibliographical note

Funding Information:
This work was supported by The Hormel Foundation and National Institutes of Health grants ZD: CA172457, CA1669011, CA827502, R37, CA081064 and by grant no. 81225013, 81430075, 2015JJ2161 in China.

Publisher Copyright:
© 2016 Macmillan Publisher Limited. All rights reserved.

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