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  • SIK2 is a centrosome kinase required for bipolar mitotic spindle formation that provides a potential target for therapy in ovarian cancer.

SIK2 is a centrosome kinase required for bipolar mitotic spindle formation that provides a potential target for therapy in ovarian cancer.

Cancer cell (2010-08-17)
Ahmed Ashour Ahmed, Zhen Lu, Nicholas B Jennings, Dariush Etemadmoghadam, Luisa Capalbo, Rodrigo O Jacamo, Nuno Barbosa-Morais, Xiao-Feng Le, Pablo Vivas-Mejia, Gabriel Lopez-Berestein, Geoffrey Grandjean, Geoffrey Bartholomeusz, Warren Liao, Michael Andreeff, David Bowtell, David M Glover, Anil K Sood, Robert C Bast
PMID20708153
ABSTRACT

Regulators 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.