Creatine kinase brain overexpression protects colorectal cells from various metabolic and non-metabolic stresses

Steven M. Mooney, Krithika Rajagopalan, Brenten H. Williams, Yu Zeng, Christhunesa S. Christudass, Youqiang Li, Bo Yin, Prakash Kulkarni, Robert H. Getzenberg

Research output: Contribution to journalArticlepeer-review


Creatine kinase brain (CKB) is one of three cytosolic isoforms of creatine kinase that is predominantly expressed in the brain. The enzyme is overexpressed in a wide variety of cancers, with the exception of colon cancer, where it is downregulated. The significance of this downregulation remains poorly understood. Here, we demonstrate that overexpression of CKB-C283S, a dominant-negative construct that lacks the kinase function but retains its ability to dimerize, causes remarkable changes in cell shape, adhesion, and invasion. Furthermore, it results in increased expression of stromal cell markers such as PAGE4 and SNAIL, suggesting an epithelial-to-mesenchymal transition (EMT) in these cells. In cells transfected with a CKB-expressing construct, CKB localizes not only to the cytosol but also to the nucleus, indicating a structural or kinase role unrelated to ATP storage. Furthermore, overexpression of CFP-tagged wild-type (WT) CKB in Caco-2 colon cancer cells dramatically increased the number of cells in G2/M but had little effect on cell proliferation. Taken together, these data demonstrate that the downregulation of CKB may play an important role in colon cancer progression by promoting EMT.

Original languageEnglish (US)
Pages (from-to)1066-1075
Number of pages10
JournalJournal of cellular biochemistry
Issue number4
StatePublished - Apr 2011
Externally publishedYes


  • Colon cancer
  • Creatine kinase brain
  • Epithelial-to-mesenchymal transition
  • Page4

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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