The Impact of Centrosome Pathologies on Prostate Cancer Development and Progression.

Abstract

The significant role of centrosomes in cancer cell proliferation has been well recognized (reviewed in Schatten H, Histochem Cell Biol 129:667-86 (2008); Schatten H, Sun Q-Y, Microsc Microanal 17(4):506-512 (2011); Schatten H, Sun Q-Y, Reprod Fertil Dev. https://doi.org/10.1071/RD14493 (2015a); Schatten H, Sun Q-Y, Centrosome-microtubule interactions in health, disease, and disorders. In: Schatten H (ed) The cytoskeleton in health and disease. Springer Science+Business Media, New York (2015b)) and new research has generated new interest and new insights into centrosomes as potential targets for cancer-specific therapies. The centrosome is a key organelle serving multiple functions through its primary functions as microtubule organizing center (MTOC) that is also an important communication center for processes involved in cellular regulation; transport to and away from centrosome-organized microtubules along microtubules is essential for cellular activities including signal transduction and metabolic activities. New research on cancer cell centrosomes has generated new insights into centrosome dysfunctions in cancer cells in which centrosome phosphorylation, balance of centrosomal proteins, centrosome regulation and duplication are impaired. Among the hallmarks of cancer cells are multipolar spindles or abnormal bipolar spindles that are formed as a result of centrosome protein expression imbalances, abnormalities in centrosome structure and abnormalities in clustering of centrosomal components that are critical for bipolar mitotic apparatus formation. Centrosome abnormalities in cancer cells can be the result of multiple factors including environmental influences and toxicants that can affect centrosome functions by inducing centrosome pathologies leading to abnormal cancer cell proliferation. These topics are addressed in this review with focus on prostate-specific therapy strategies to target centrosome abnormalities. We will also address loss of cell polarity in cancer cells in which centrosome dysfunctions play a role as well as the loss of primary cilia in prostate cancer development and progression.