Author/Authors :
Ahmed، نويسنده , , Ahmed Ashour and Lu، نويسنده , , Zhen and Jennings، نويسنده , , Nicholas B. and Etemadmoghadam، نويسنده , , Dariush and Capalbo، نويسنده , , Luisa and Jacamo، نويسنده , , Rodrigo O. and Barbosa-Morais، نويسنده , , Nuno and Le، نويسنده , , Xiao-Feng and Vivas-Mejia، نويسنده , , Pablo and Lopez-Berestein، نويسنده , , Gabriel and Grandjean، نويسنده , , Geoffrey and Bartholomeusz، نويسنده , , Geoffrey and Liao، نويسنده , , Warren and Andreeff، نويسنده , , Michael and Bowtell، نويسنده , , David and Glover، نويسنده , , David M. and Sood، نويسنده , , Anil K. and Bast Jr.، نويسنده , , Robert C.، نويسنده ,
Abstract :
Summary
tors of mitosis have been successfully targeted to enhance response to taxane chemotherapy. Here, we show that the salt inducible kinase 2 (SIK2) localizes at the centrosome, plays a key role in the initiation of mitosis, and regulates the localization of the centrosome linker protein, C-Nap1, through S2392 phosphorylation. Interference with the known SIK2 inhibitor PKA induced SIK2-dependent centrosome splitting in interphase while SIK2 depletion blocked centrosome separation in mitosis, sensitizing ovarian cancers to paclitaxel in culture and in xenografts. Depletion of SIK2 also delayed G1/S transition and reduced AKT phosphorylation. Higher expression of SIK2 significantly correlated with poor survival in patients with high-grade serous ovarian cancers. We believe these data identify SIK2 as a plausible target for therapy in ovarian cancers.
