The role of centrosome over-duplication in liver cancer

Abstract

Centrosome, which is the microtubule-organising center (MTOC) in the cell, plays a critical role in determining the motility, polarity and division of cell. Strong evidence suggests that supernumerary centrosomes drive chromosomal instability and is linked to oncogenesis. While aneuploidy is frequently observed in human cancer cells, targeting the cancer cells with dysregulated centrosome function may represent a novel approach of cancer therapy. In general, there are four major groups of centrosome kinase, including Polo-like kinase (PLK), Aurora kinase, Cyclin-dependent protein kinase (CDK) and NIMA-related kinase (NEK), that are believe to play important role in regulating centrosome activity, cell cycle progression and cell polarity. Interestingly, emerging evidence has shown that inhibitors of these kinases have significant effect in inhibiting cancer cell growth. Recently, we have characterized a novel centrosome protein, we named TAX1BP2, which plays a critical role in blocking centrosome over-duplication. TAX1BP2 is also targeted by human T cell leukaemia virus (HTLV-I) to create chromosome instability and aneuploidy. We showed that TAX1BP2 is a putative tumor suppressor in liver cancer (hepatocellular carcinoma, HCC) and is regulated by CDK2 kinase. We also observed that several centrosome kinases, including PLK4 and NEK2, were deregulated in HCC and may regulate TAX1BP2 by phosphorylation. Thus, these results suggest that targeting centrosome kinase may represent a novel approach for liver as well as other cancer therapy.