Mitosis: Chromosome Segregation and Stability

Abstract

Mammalian cells are charged with the task of evenly distributing 46 chromosomes to each of two daughter cells during every mitotic cell division. This is achieved by a microtubule‐based cellular structure termed the mitotic spindle. However, numerous cellular and/or genetic defects are known to impair the fidelity of mitosis and promote chromosome segregation errors and aneuploidy. Missegregation of even a single chromosome leads to the deregulated expression of hundreds to thousands of genes, including many that are involved in essential processes such as DNA replication, repair and mitosis. Consequently, while aneuploidy is most typically detrimental to cell viability, it also has the potential to initiate a self‐propagating cycle of chromosome instability that can ultimately promote tumour initiation, progression and relapse. Key Concepts Chromosome segregation is driven by the mitotic spindle. Multiple genetic and/or cell biological defects are known to cause chromosome missegregation and aneuploidy. Aneuploidy is poorly tolerated in normal cells. Cancer cells adapt to tolerate aneuploidy. Cells that persistently missegregate chromosomes are termed chromosomally unstable (CIN). CIN promotes tumour initiation, progression and relapse and correlates with poor patient prognosis. Aneuploidy and CIN are hallmarks of human tumours.

KIF18B promotes tumor progression through activating the Wnt/β-catenin pathway in cervical cancer

“… 27 Abnormal expression of the KIF18A protein leads to sister chromosome separation abnormalities, subsequently causing cell aneuploidy, and ultimately inducing tumor. 28 Several studies have reported that KIF18A is closely related to breast cancer, stomach cancer, and renal cancer. 29 – 31…”