A spindle turned perpendicular (bottom) to the surface leaves only one daughter on the matrix.


A misoriented mitotic spindle may be a short cut to metastasis, based on results from Jurii Vasiliev (Moscow State University, Russia), Edward Bonder (Rutgers University, Newark, NJ), and colleagues.

Cells in an epithelial layer normally divide perpendicular to their surface; each daughter cell thus remains in contact with the matrix and surrounding cells. The new results show that cells with too much RhoA activity, as found in several cancer cell lines, lost the spindle orientation needed for this perpendicular division. Many of the cells thus made a spindle that left only one daughter on the matrix.

The other cell, atop its matrix-bound sister, lacked the spread phenotype of matrix-attached cells. Due to inadequate cell–cell adhesions, these rounded cells occasionally detached from the epithelium, floated off in the medium, and settled at new sites.

Cells with overactive RhoA were more contracted and had altered actin networks suggestive of hyperactive myosin II. Blocking myosin II activity reversed the RhoA effects. Bonder now wonders, “does myosin II activity alter the movement of the formed spindle relative to the cell itself, or is the process of forming the spindle aberrant from the very start?”

The results suggest that cancerous cells may not have to acquire the ability to migrate to metastasize. “[Unregulated] cell division would lead not only to increased tumor mass,” says Bonder, “but could also be squirting out cells.” Circulatory flow could then sweep off some of these cells and deposit them elsewhere. ▪


Vasiliev, J.M., et al. 2004. Proc. Natl. Acad. Sci. USA. doi:.