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Cancer Cell. 2010 Aug 9;18(2):109-21. doi: 10.1016/j.ccr.2010.06.018.

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

Author information

1
Department of Experimental Therapeutics, M.D. Anderson Cancer Center, University of Texas, Houston, 77030, USA. ahmed.ahmed@obs-gyn.ox.ac.uk

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.

PMID:
20708153
PMCID:
PMC3954541
DOI:
10.1016/j.ccr.2010.06.018
[Indexed for MEDLINE]
Free PMC Article

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