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maintenance of the bipolar mitotic spindle that require to accurately divide genetic material (chromosomes)
into daughter cells during cell division. Centrosome aberrations are either numerical or structural aberrations
since they arise when centrosome structure, duplication or segregation are deregulated. So far, it has not
been shown whether structural centrosome aberrations directly trigger drug resistance. In this review, we
only focus on numerical aberrations of centrosome. Acquisition of ≥ 3 centrosomes in the centrosome cycle
was termed centrosome amplification. Failure to properly control centrosome number leads to aneuploidy,
which is frequently found in cancer cells. Mechanistically centrosome amplification may cause multipolar
spindles or monopolar aster resulting in chromosome missegregation . Thus, centrosome amplification is a
[4]
hallmark of human tumors [5-10] . The BRCA1 E3 ligase specifically ubiquitinated γ-tubulin at lysine-48 (K48)
and the expression of a mutant γ-tubulin protein in which K48 was mutated to arginine induces centrosome
amplification . However, centrosome amplification does not necessarily require DNA damages, epigenetic
[11]
changes is one potential mechanistic link in dysregulation of centrosome function. Here we discuss in detail
on centrosome structure, aberrations of centrosome in cancer, the relationship of cancer drug resistance to
centrosome amplification and new drug development.

CENTROSOME ABERRATIONS, CANCER AND CANCER DRUG RESISTANCE
In this section, we briefly summarize the structure and biogenesis of centrosomes (for more detail reviews,
please refer to . Morphologically, centrosomes are non-membranous organelles. Each centrosome consists
[12]
of a pair of centrioles surrounded by the pericentriolar material (PCM) [Figure 1]. Although molecular
compositions of the centrosome remain poorly defined, hundreds of proteins have been detected using
proteomics [13,14] . As illustrated in Figure 2 , cycling cells begin the cell cycle with one centrosome in G1,
[15]
and centriole duplication occurs once per cell cycle, paralleled with DNA replication during the S phase.
The duplication of the centrosome is initiated (formation of the procentriole) with Plk4 as the dominant
kinase in centriole biogenesis [16,17] . Depletion of Plk4 induces the loss of centrioles and overexpression of Plk4
conversely causes the formation of multi-daughter centrioles .
[18]

Once centrioles are assembled, PCM proteins will be recruited, nucleating more microtubules during
interphase. These proteins are not only important for centrosome biogenesis but also contribute to the
maintenance of cell polarity, cell vesicle transport, cell adhesion, cell signal transduction (Reviewed ).
[19]
Duplicated centrosomes separate at the onset of mitosis for bipolar spindle formation, which equally
segregate sister chromatids to two daughter cells. Centrosome disjunction is modulated by NEK2a to remove
centrosomal linkers, such as C-Nap1 (also known as CEP250) and rootletin ). Over-expression of NEK2a
[20]
induces immature centrosome separation [21,22] .

It is worth to note that majority of centrosome proteins have multiple locations. Approximately 77% (n = 370) of
the centrosome and microtubule-organizing center (MTOC) proteins detected in the cell atlas also localize
to other cellular compartments . The network plot shows that the most common locations shared with
[23]
centrosome and MTOC are the cytoplasm, nucleus and vesicles. For example, CTCF is associated with the
centrosome in metaphase to anaphase of the cell cycle. At telophase, CTCF dissociates from the centrosome
and localizes to the midbody and the newly formed nuclei.

Functionally the centrosome in human cells acts as the MTOC, which has been studied widely ever since
first described by Theodor Bovery in 1900 , and the actin-organizing center . Importantly precisely
[24]
[25]
duplicated and matured centrosomes ensure faithful chromosome segregation into two daughter cells via
the formation of the bipolar mitotic spindle . Thus, when centrosome structure, duplication or segregation
[26]
are deregulated, centrosome aberrations with either numerical or structural aberrations arise.
Many studies established a link of centrosome aberrations and solid tumors or hematological malignancies;
the correlations are present not only in pre-invasive lesions but also with tumor progression [27,28] . Althoug