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

AA Ahmed, Z Lu, NB Jennings, D Etemadmoghadam… - Cancer cell, 2010 - cell.com
AA Ahmed, Z Lu, NB Jennings, D Etemadmoghadam, L Capalbo, RO Jacamo…
Cancer cell, 2010cell.com
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 …
Summary
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.
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