Living in CIN: Mitotic Infidelity and Its Consequences for Tumor Promotion and Suppression

• Published in: Developmental cell 2016-12, Vol.39 (6), p.638-652
• Main Authors: Funk, Laura C., Zasadil, Lauren M., Weaver, Beth A.
• Format: Article
• Language: English
• Subjects: Aneuploidy; Animals; Carcinogenesis - pathology; Chromosomal Instability; CIN; Humans; Mitosis; mitotic checkpoint; Models, Biological; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - pathology; spindle assembly checkpoint; Tumor Suppressor Protein p53 - metabolism
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2016.10.023

Errors in chromosome segregation during mitosis have been recognized as a hallmark of tumor cells since the late 1800s, resulting in the long-standing hypothesis that mitotic abnormalities drive tumorigenesis. Recent work has shown that mitotic defects can promote tumors, suppress them, or do neither, depending on the rate of chromosome missegregation. Here we discuss the causes of chromosome missegregation, their effects on tumor initiation and progression, and the evidence that increasing the rate of chromosome missegregation may be an effective chemotherapeutic strategy. Errors in chromosome segregation are a hallmark of tumor cells. Furthermore, how mitotic defects affect tumors depends on the rate of chromosome missegregation. Funk et al. discuss causes of chromosome missegregation, their effects on tumor initiation and progression, and whether increasing chromosome missegregation rates may be an effective chemotherapeutic strategy.