TY - JOUR
T1 - Chromosomal instability
T2 - A common feature and a therapeutic target of cancer
AU - Tanaka, Kozo
AU - Hirota, Toru
N1 - Funding Information:
We apologize to our colleagues whose work was not mentioned in this review due to space limitations. Laboratories of K.T. and T.H. are supported by Grants-in- Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS; Grant Number 15H04368 , 16K14604 , 15H02365 , 24370076 ); Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT; Grant Number 26114702 , 15H05977 , 26114718 , 26116523 ). K.T. acknowledges a grant from Takeda Science Foundation.
Publisher Copyright:
© 2016 Elsevier B.V.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - Most cancer cells are aneuploid, containing abnormal numbers of chromosomes, mainly caused by elevated levels of chromosome missegregation, known as chromosomal instability (CIN). These well-recognized, but poorly understood, features of cancers have recently been studied extensively, unraveling causal relationships between CIN and cancer. Here we review recent findings regarding how CIN and aneuploidy occur, how they affect cellular functions, how cells respond to them, and their relevance to diseases, especially cancer. Aneuploid cells are under various kinds of stresses that result in reduced cellular fitness. Nevertheless, genetic heterogeneity derived from CIN allows the selection of cells better adapted to their environment, which supposedly facilitates generation and progression of cancer. We also discuss how we can exploit the properties of cancer cells exhibiting CIN for effective cancer therapy.
AB - Most cancer cells are aneuploid, containing abnormal numbers of chromosomes, mainly caused by elevated levels of chromosome missegregation, known as chromosomal instability (CIN). These well-recognized, but poorly understood, features of cancers have recently been studied extensively, unraveling causal relationships between CIN and cancer. Here we review recent findings regarding how CIN and aneuploidy occur, how they affect cellular functions, how cells respond to them, and their relevance to diseases, especially cancer. Aneuploid cells are under various kinds of stresses that result in reduced cellular fitness. Nevertheless, genetic heterogeneity derived from CIN allows the selection of cells better adapted to their environment, which supposedly facilitates generation and progression of cancer. We also discuss how we can exploit the properties of cancer cells exhibiting CIN for effective cancer therapy.
KW - Aneuploidy
KW - Cancer
KW - Chromosomal instability
KW - Chromosome segregation
KW - Kinetochore
KW - Mitosis
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U2 - 10.1016/j.bbcan.2016.06.002
DO - 10.1016/j.bbcan.2016.06.002
M3 - Review article
C2 - 27345585
AN - SCOPUS:84976416919
SN - 0304-419X
VL - 1866
SP - 64
EP - 75
JO - Biochimica et Biophysica Acta - Reviews on Cancer
JF - Biochimica et Biophysica Acta - Reviews on Cancer
IS - 1
ER -