Author(s): Chen Y, Kong Q
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Abstract Although great effort has been made, the understanding of the mechanisms of hepatocarcinogenesis is still limited. Among all the related hypotheses, the cell brain theory, which emphasized the integrate roles of the complex consisting of centrosome, the embedded centrioles and connecting microtubules (MTs) and interpreted cancer as a cell brain illness rather than a genetic disease, emerges to be more logic and recognizable. According to cell brain theory, all the cellular procedures are coordinated as a whole by the "brain" of a cell determining a cell's fate. Structural and functional abnormalities in the cell brain may result in unequal or multipolar segregation of the chromosomes, thereby causing cell cycle disorder, centrosome amplification, and genomic instability. Although there lacking of direct evidence associating cell brain defects and hepatocarcinogenesis, latest understanding of the roles of the cells brain in cell control does teach us that any defects in the cell brain may contribute to hepatocarcinogenesis. Briefly, more than 100 key proteins involved in DNA synthesis, DNA repair, cell cycle, and apoptosis have been localized to the cell brain. Specifically, more and more novel proteins associated with centrosome such as centrin, centriolin and cenexin are located in the centriole, a core component of cenrtrosome. Aberrant phosphorylation of these proteins and/or mutation of the coding genes may inevitably cause supernumerary centrioles and/or excess pericentriolar material. Modifications of any MT proteins such as tyrosinated tubulin (Tyr-tubulin), detyrosinated tubulin (Glu-tubulin) and Delta2-tubulin may change the structure and function of MTs, thereby interfering with G1 phase progression, altering the dynamics of some key proteins, and mis-regulating signal transduction and transcription. Although little work has been done, we intend to believe, based on the latest understanding of the novel roles of the cell brain in cell control, that defects in any part of the cell brain either in the structure or in the function may result in changes of the genes, eventually leading to the development of liver cancer, which is discussed in this paper and is expected to be helpful in shedding light on the often paradoxical observations seen in the development of cancer, including HCC. It also teaches us that when treating cancerous problems therapeutically or prophylactically, great attention should be given to the centrosome/cell brain, instead of gene alone. More specifically, the centrosome-centered cell brain may come to be novel targets in the treatment of cancer including HCC.
This article was published in Med Hypotheses
and referenced in Journal of Cell Science & Therapy