Cystic fibrosis as a bowel cancer syndrome and the potential role of CK2.
Chloride is critical in creating differential pH values inside various organelles (Golgi for example) by linking ATP hydrolysis to trans-bilayer proton movement. This proton-ATPase drives anions such as chloride through unrelated channels in the endosomal/organellar bilayer thus loading HCl into different lipid-encased cellular compartments. Critically, intraorganellar pH (and ion channel content/activities) differs during different phases of the cell cycle. The cystic fibrosis (CF) chloride channel protein CFTR is a member of the ABC family (ABCC7) and resides in many endosomal membranes trafficking to the epithelial surface and back again. Recently, it has become clear that human CF has an unusually high incidence of cancer in the bowel with correspondingly elevated gut epithelial proliferation rates observed in CF mice. In this review, emphasis is placed on CK2 & CF because CK2 controls not only proliferation but also four different members of the ABC superfamily including the multi-drug resistance protein P-glycoprotein and CFTR itself. In addition, CK2 also regulates a critical cancer-relevant and CFTR-regulated cation channel (ENaC) that mediates the cellular accumulation of sodium ions within epithelia such as the colon and lung. Not only are ENaC and CFTR both abnormal in CF cells, but ENaC also 'carries' CK2 to the cell membrane in oocytes, only provided its two target phosphosites are intact. CK2 may be a critical regulator of cell proliferation in conjunction with regulation of ion channels such as CFTR, other ABC members and the cation channel ENaC. The emerging idea is that CFTR may control membrane-CK2 as much as membrane-CK2 controls CFTR.
Mehta
Anil
A
Division of Maternal and Child Health Sciences, Ninewells Hospital, University of Dundee, Dundee, DD1 9SY, UK. a.mehta@dundee.ac.uk
D000818:Animals; D047390:Casein Kinase II / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000150:complications* / Q000201:enzymology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D005770:Gastrointestinal Neoplasms / Q000150:complications* / Q000201:enzymology*; D006801:Humans; D013577:Syndrome
D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D047390:Casein Kinase II