Microtubule Tethers at Kinetochores and Spindle Poles: Essential Mitotic Components

Disruption of kinetochore function leading to reduced microtubule attachment and decreased checkpoint signaling results in the gain or loss of whole chromosomes (aneuploidy), which is a hallmark of cancer. However, whether aneuploidy is a cause or effect of tumorigenesis has remained untested since it was first suggested as an agent of carcinogenesis more than 100 years ago. Heterozygosity for the microtubule-binding, kinetochore localized, kinesin-like motor protein, CENP-E, results in the development of aneuploidy in cultured cells and in vivo in the absence of additional genomic instability. A variety of studies presented here, using CENP-E heterozygous animals, demonstrate that elevated rates of chromosome segregation errors act in a context dependent manner to either promote or inhibit tumorigenesis.