Centrosomal Protein 55 increases chromosomal instability in ovarian cancer cells by controlling microtubule dynamics

Centrosomal Protein 55 (CEP55) exhibits different oncogenic activities; it regulates the PI3K-Akt-pathway, cellular abscission and chromosomal instability (CIN) in cancer cells. While the mechanism of CEP55-controlled PI3K-Akt signaling and cellular abscission are well-understood, its role in CIN has not been elucidated yet. Thus, the focus of this study was to address this issue. Depletion of CEP55 in ovarian cancer cells decreased the CIN rate, increased spindle microtubule-dynamics and decreased spindle microtubule-stability. In addition, recombinant CEP55 accelerated microtubule-polymerization and attenuated cold-induced microtubule-depolymerization. To analyze a potential relationship between CEP55 controlled CIN and its impact on microtubule-dynamics, the CEP55 microtubule-binding peptides were identified and a mutant with deficient microtubule-binding activity re-expressed in CEP55 depleted cells. This mutant did not restore decreased CIN in CEP55 depleted cells, indicating that CEP55 controls CIN by binding MTs. This knowledge now provides the possibility to selectively interfere with CEP55 controlled CIN in cancer cells.