Key Points
- Researchers discovered that two proteins, KIF18A and CENP-E, work together to align chromosomes during cell division.
- Blocking both of these proteins simultaneously selectively kills cancer cells. This discovery could lead to a new, targeted cancer therapy.
- The study found that some cancer cells are especially vulnerable because they naturally have low levels of CENP-E.
- Measuring CENP-E levels in tumors could help doctors predict which patients will respond best to certain drugs.
Researchers have discovered a new way that cells line up their chromosomes during cell division, and it could lead to a promising new cancer treatment. Published in Cell Reports, a team from the University of Osaka and the Massachusetts Institute of Technology found that two key motor proteins, KIF18A and CENP-E, work together to make sure chromosomes align properly. When both of these proteins are blocked simultaneously, it selectively kills cancer cells.
For cells to divide healthily, they need to separate their chromosomes accurately. When this process fails, it causes “chromosomal instability,” which is a common feature of cancer. The researchers were trying to understand the exact mechanisms behind this process.
Using a special cell line with a slightly defective kinetochore, the team screened for genetic weaknesses. They found that these cells died when the KIF18A gene was turned off. They then discovered that these same cells also had low levels of another motor protein, CENP-E.
This led them to a key finding: KIF18A and CENP-E work together to ensure that chromosomes line up correctly in the middle of a cell. In normal, healthy cells, if one of these proteins isn’t working well, the other can often pick up the slack. But when both are impaired, the whole process fails, and the cell dies.
Crucially, the team found that cancer cells that are sensitive to KIF18A inhibitors naturally have low levels of CENP-E. This explains why these drugs are so effective against certain types of cancer.
This discovery suggests that doctors could measure CENP-E levels in tumors to identify which cancers will respond best to KIF18A-blocking drugs. It also hints that combining drugs that affect both of these proteins could make cancer treatments even more effective.
“We not only uncovered detailed mechanisms of chromosome segregation but also applied these findings to kill cancer cells efficiently,” said senior author Professor Tatsuo Fukagawa.
