Centrosome amplification is frequently observed in aggressive human cancers, and it has been proposed as a promising target in cancer therapy. Work by Mariappan et al (2019) in this issue details the identification of a small‐molecule inhibitor that perturbs the CPAP–tubulin interaction, prevents efficient centrosome clustering during mitosis, and exhibits in vivo anti‐tumor activity. This study demonstrates the potential of developing tumor‐specific treatment by specifically targeting centrosome amplification.
See also: A Mariappan et al (January 2019)
As the primary microtubule‐organizing center of cells, centrosomes play primordial roles in a number of cellular processes that include cell signaling, motility, and the regulation of cell shape and polarity. Centrosomes are composed of an orthogonally arranged pair of ninefold symmetric centrioles, surrounded by pericentriolar material (PCM). PCM harbors cell cycle regulators and proteins involved in microtubule nucleation and mitotic spindle assembly, contributing to a commitment of accurate cell division (Nigg & Holland, 2018). To maintain those functions, centrosome must be duplicated once and only once per cell cycle, and alterations in this process contribute to many human disorders including cancer and microcephaly (Nigg & Holland, 2018).
A wide range of human cancers display prominent numerical and structural centrosomal aberrations (Prosser & Pelletier, 2017). Centrosome loss, through a failure of centriole duplication, in normal cells leads to robust cell cycle arrest, whereas cancer cells can survive and circumvent this surveillance pathway by inhibiting p53 function (Lambrus …
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