Mitotic Regulator Hec1 as a Potential Target for Cancer Therapy

Studies on mitosis have provided abundant molecular and biochemical insights into this highly complex stage of the cell cycle. During mitosis, cells employ a multitude of factors to orchestrate spindle formation and chromosome movement in coordination with proper spindle checkpoint control. Functional perturbation or inactivation of these mitotic regulators often triggers abnormal mitotic progression, which may consequently lead to mitotic catastrophe and cell death. Because cancer cells are highly proliferative, mitotic disruption has become a useful strategy for cancer therapeutic intervention. One important mitotic regulator, Hec1 (highly expressed in cancer 1), plays an essential role in mitotic progression through its function in proper spindle assembly. Our laboratory has developed small molecule inhibitors (INH) that disrupt the interaction between Hec1 and Nek2. Treatment with these compounds leads to drastic abnormalities in chromosome segregation, spindle assembly, and eventual cancer cell death. Importantly, INH inhibits tumor growth in a nude mouse model with no adverse side effects. Our results demonstrate a novel method of cancer cell-specific mitotic inhibition by an innovative class of compounds that warrant further development.