title: Creatine kinase brain overexpression protects colorectal cells from various metabolic and non-metabolic stresses.
abstract: 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.
authors.affiliation: Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Mooney
authors.forename: Krithika
authors.initials: K
authors.lastname: Rajagopalan
authors.forename: Brenten H
authors.initials: BH
authors.lastname: Williams
authors.forename: Yu
authors.initials: Y
authors.lastname: Zeng
authors.forename: Christhunesa S
authors.initials: CS
authors.lastname: Christudass
authors.forename: Youqiang
authors.initials: Y
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Yin
authors.forename: Prakash
authors.initials: P
authors.lastname: Kulkarni
authors.forename: Robert H
authors.initials: RH
authors.lastname: Getzenberg
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D018938:Caco-2 Cells; D002453:Cell Cycle; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D052276:Creatine Kinase, BB Form / Q000235:genetics* / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D015151:Immunoblotting; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D013312:Stress, Physiological; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D008164:Luminescent Proteins; C474505:PAGE4 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin; D058570:TOR Serine-Threonine Kinases; D052276:Creatine Kinase, BB Form