Suppressive role of fukutin on cell proliferation in uterine cervical carcinoma in relation to Aurora-A kinase.

Abstract

Fukutin, the gene responsible for Fukuyama congenital muscular dystrophy (FCMD), is involved in the glycosylation of α-dystroglycan (α-DG). On the other hand, fukutin is expressed in various organs, and the roles of fukutin in non-neuromuscular tissues are not fully elucidated. In the present immunohistochemical study of uterine cervical carcinoma, Ki-67-positive cells tended to be more in areas showing weaker expression of fukutin. In HeLa cells, Ki-67-positive cells were increased after the suppression of fukutin by RNAi, and were decreased by overexpression of fukutin. Similar results were obtained upon phosphorylation of histone H3 at serine 10, which is enriched during mitosis. Interestingly, Aurora-A kinase (AURKA), one of the proteins regulating Ser10 phosphorylation of histone H3, was highly expressed in HeLa cells, and the phosphorylation of AURKA was reduced by overexpression of fukutin. Furthermore, fukutin is co-localized with targeting protein for Xklp2 (TPX2), a protein enhancing AURKA activity. Fukutin may be able to suppress cell proliferation by reducing AURKA phosphorylation, probably competing with TPX2.