Attenuated Chromosome Oscillation as a Cause of Chromosomal Instability in Cancer Cells

SIMPLE SUMMARY: Chromosomal instability (CIN), a condition in which chromosome missegregation occurs at high rates, is widely seen in cancer cells. Causes of CIN in cancer cells are not fully understood. A recent report suggests that chromosome oscillation, an iterative chromosome motion typically seen in metaphase around the spindle equator, is attenuated in cancer cells, and is associated with CIN. Chromosome oscillation promotes the correction of erroneous kinetochore-microtubule attachments through phosphorylation of Hec1, a kinetochore protein that binds to microtubules, by Aurora A kinase residing on the spindle. In this review, we focused on this unappreciated link between chromosome oscillation and CIN. ABSTRACT: Chromosomal instability (CIN) is commonly seen in cancer cells, and related to tumor progression and poor prognosis. Among the causes of CIN, insufficient correction of erroneous kinetochore (KT)-microtubule (MT) attachments plays pivotal roles in various situations. In this review, we focused on the previously unappreciated role of chromosome oscillation in the correction of erroneous KT-MT attachments, and its relevance to the etiology of CIN. First, we provided an overview of the error correction mechanisms for KT-MT attachments, especially the role of Aurora kinases in error correction by phosphorylating Hec1, which connects MT to KT. Next, we explained chromosome oscillation and its underlying mechanisms. Then we introduced how chromosome oscillation is involved in the error correction of KT-MT attachments, based on recent findings. Chromosome oscillation has been shown to promote Hec1 phosphorylation by Aurora A which localizes to the spindle. Finally, we discussed the link between attenuated chromosome oscillation and CIN in cancer cells. This link underscores the role of chromosome dynamics in mitotic fidelity, and the mutual relationship between defective chromosome dynamics and CIN in cancer cells that can be a target for cancer therapy.