Title of article
SIK2 Is a Centrosome Kinase Required for Bipolar Mitotic Spindle Formation that Provides a Potential Target for Therapy in Ovarian Cancer
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 ,
Issue Information
روزنامه با شماره پیاپی سال 2010
Pages
13
From page
109
To page
121
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.
Keywords
CELLCYCLE , HUMDISEASE , CELLBIO
Journal title
Cancer Cell
Serial Year
2010
Journal title
Cancer Cell
Record number
1337210
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