Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
J Cell Biochem. 2011 Apr;112(4):1066-75. doi: 10.1002/jcb.23020.
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.
脑型肌酸激酶（CKB）是肌酸激酶三种胞质同工酶之一，主要在大脑中表达。该酶在多种癌症中过表达，但结肠癌除外，在结肠癌中其表达下调。这种下调的意义仍知之甚少。在这里，我们证明了 CKB-C283S 的过表达会导致细胞形状、黏附和侵袭发生显著变化，CKB-C283S 是一种显性负性构建体，缺乏激酶功能但保留其二聚化能力。此外，它还导致间质细胞标志物如 PAGE4 和 SNAIL 的表达增加，表明这些细胞发生上皮间质转化（EMT）。在转染 CKB 表达构建体的细胞中，CKB 不仅定位在细胞质中，还定位在细胞核中，表明其结构或激酶功能与 ATP 储存无关。此外，CFP 标记的野生型（WT）CKB 在 Caco-2 结肠癌细胞中的过表达显著增加了 G2/M 期的细胞数量，但对细胞增殖几乎没有影响。总之，这些数据表明，CKB 的下调可能通过促进 EMT 在结肠癌进展中发挥重要作用。
