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Page 212 Jia et al. Cancer Drug Resist 2019;2:210-24 I http://dx.doi.org/10.20517/cdr.2018.010
Figure 1. Centrosome structure. A: the centrosome consists a pair of orthogonal centrioles, surrounded by mass proteins, referred
to as the pericentriolar material (PCM). PCM proteins subdivide the PCM to three layers depending on diameter of the ring-like
structures. Mother centrioles possess subdistal appendages and distal appendages; B: each centriole is a cylindrical structure with
nine-fold microtubule organized like a central cartwheel. The triplet microtubules are composed of internal A, middle B, and external C
microtubules. The figure is adapted and modified [9]
bipolar spindles could be detected in centrosome depletion or centrosome over-duplicated cells by clustering
mechanisms , the numerical centrosome aberrations are still the most common cause for chromosomal
[29]
segregation errors . Centrosome amplification thus can be as a novel biomarker for personalized treatment
[30]
of cancers . Several oncogenic and tumor suppressor proteins, such as BRCA1 and p53, are the best-known
[31]
centrosome proteins [32,33] . Either overexpression or downregulation of centrosome proteins evoke centrosome
abnormalities resulting tumorigenesis [Table 1].
As discussed above, NEK2 is an important centrosome protein, which regulates centrosome separation and
bipolar spindle formation in mitotic cells. High expression of NEK2 also mediates drug resistance to cisplatin
or lipo-doxorubicin in myeloma , breast cancer , ovarian cancer and liver cancer . Nlp (ninein-like
[48]
[49]
[51]
[50]
protein) is involved in centrosome maturation and spindle formation. Nlp overexpression was detected in
human breast and lung cancers . By examining 55 breast cancer samples, a study found that the breast
[52]
cancer patients with high expression of Nlp were likely resistant to the treatment of paclitaxel. KIFC1 is a
nonessential minus end-directed motor of the kinesin-14 family and it functions as a centrosome clustering
molecule [53,54] . In breast cancer cells, overexpression of KIFC1 and KIFC3 confer docetaxel resistance .
[55]