TY - JOUR
T1 - Attenuated chromosome oscillation as a cause of chromosomal instability in cancer cells
AU - Iemura, Kenji
AU - Yoshizaki, Yujiro
AU - Kuniyasu, Kinue
AU - Tanaka, Kozo
N1 - Funding Information:
This research was funded by JSPS KAKENHI grant numbers 16H06635 and 18K15234, grants from Uehara Memorial Foundation, Kanae Foundation for the Promotion of Medical Science, and Gonryo Medical Foundation to K.I., and JSPS KAKENHI grant numbers 16K14604 and 18H02434, and a grant from the Takeda Science Foundation to K.T. The authors thank members of the K.T. laboratory for discussions.
Funding Information:
and Gonryo Medical Foundation to K.I., and JSPS KAKENHI grant numbers 16K14604 and 18H02434, and a grant from the Takeda Science Foundation to K.T.
Publisher Copyright:
© 2021 by the authorsLicensee MDPI, Basel, Switzerland.
PY - 2021/9
Y1 - 2021/9
N2 - Chromosomal instability (CIN) is commonly seen in cancer cells, and related to tumor progression and poor prognosis. Among the causes of CIN, insufficient correction of erroneous kinetochore (KT)-microtubule (MT) attachments plays pivotal roles in various situations. In this review, we focused on the previously unappreciated role of chromosome oscillation in the correction of erroneous KT-MT attachments, and its relevance to the etiology of CIN. First, we provided an overview of the error correction mechanisms for KT-MT attachments, especially the role of Aurora kinases in error correction by phosphorylating Hec1, which connects MT to KT. Next, we explained chromosome oscillation and its underlying mechanisms. Then we introduced how chromosome oscillation is involved in the error correction of KT-MT attachments, based on recent findings. Chromosome oscillation has been shown to promote Hec1 phosphorylation by Aurora A which localizes to the spindle. Finally, we discussed the link between attenuated chromosome oscillation and CIN in cancer cells. This link underscores the role of chromosome dynamics in mitotic fidelity, and the mutual relationship between defective chromosome dynamics and CIN in cancer cells that can be a target for cancer therapy.
AB - Chromosomal instability (CIN) is commonly seen in cancer cells, and related to tumor progression and poor prognosis. Among the causes of CIN, insufficient correction of erroneous kinetochore (KT)-microtubule (MT) attachments plays pivotal roles in various situations. In this review, we focused on the previously unappreciated role of chromosome oscillation in the correction of erroneous KT-MT attachments, and its relevance to the etiology of CIN. First, we provided an overview of the error correction mechanisms for KT-MT attachments, especially the role of Aurora kinases in error correction by phosphorylating Hec1, which connects MT to KT. Next, we explained chromosome oscillation and its underlying mechanisms. Then we introduced how chromosome oscillation is involved in the error correction of KT-MT attachments, based on recent findings. Chromosome oscillation has been shown to promote Hec1 phosphorylation by Aurora A which localizes to the spindle. Finally, we discussed the link between attenuated chromosome oscillation and CIN in cancer cells. This link underscores the role of chromosome dynamics in mitotic fidelity, and the mutual relationship between defective chromosome dynamics and CIN in cancer cells that can be a target for cancer therapy.
KW - Aneuploidy
KW - Aurora kinase
KW - Cancer
KW - Chromosomal instability
KW - Chromosome oscillation
KW - Hec1
KW - Kinetochore-microtubule attachment
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U2 - 10.3390/cancers13184531
DO - 10.3390/cancers13184531
M3 - Review article
AN - SCOPUS:85114520378
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 18
M1 - 4531
ER -