4.6 Review

Chromosomal instability: A common feature and a therapeutic target of cancer

Journal

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
Volume 1866, Issue 1, Pages 64-75

Publisher

ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbcan.2016.06.002

Keywords

Chromosomal instability; Aneuploidy; Cancer; Chromosome segregation; Kinetochore; Mitosis

Funding

  1. Japan Society for the Promotion of Science (JSPS) [15H04368, 16K14604, 15H02365, 24370076]
  2. Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) [26114702, 15H05977, 26114718, 26116523]
  3. Takeda Science Foundation
  4. Grants-in-Aid for Scientific Research [15H05977, 16K14604, 26116523, 16H01296, 26114702, 26114718, 15H02365, 15H04368] Funding Source: KAKEN

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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. (C) 2016 Elsevier B.V. All rights reserved.

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