The APC–tumor connection

Chromosomal instability—the less than faithful mitotic segregation of chromosomes—is a hallmark of several cancers, particularly colorectal tumors. Also common in these tumors is a mutation that truncates the adenomatous polyposis coli (APC) protein. On page 949, Green and Kaplan show that this is more than coincidence—APC truncations lead to defective mitotic spindles resembling those of colorectal tumor cells.

The faulty spindles are a result of defective capture of microtubule plus ends. The authors expressed the truncated APC protein in noncancerous cell lines that also had normal APC and found that, in these cells, spindle microtubles could no longer grab hold of the kinetochores. This caused chromosome misalignment and segregation defects. Astral microtubules were lost, presumably because they were not stabilized by interactions with the cell cortex. Without complete asters, spindles were free floating and...