Heparanase Is a Critical Regulator of Mitotic Spindles Required for Maintaining Chromosome Stability.

The mitotic spindle, assembled by microtubule organization center (MTOC), is a critical structure required for proper chromosome segregation during mitosis. Studies demonstrated that defects of mitotic spindle assembling would result in chromosome instability, associating with oncogenesis. In this study, we identified that heparanase (HPSE) was localized on MTOC in mitotic cells. Induced expression of HPSE in human airway epithelial cells promoted mitotic spindle formation, and silencing of HPSE expression disrupted the mitotic spindle formation, resulting in chromosome instability, including chromosome mis-segregation and increased micronuclei formation. In conclusion, HPSE is an important protein in regulation of mitotic spindle and loss of HPSE function on MTOC associates with chromosome instability, indicating that loss of HPSE on MTOC may play critical roles in oncogenesis.