2. Academic Validation
  3. 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 Aug 9;18(2):109-21. doi: 10.1016/j.ccr.2010.06.018.
Ahmed Ashour Ahmed 1,  Zhen Lu,  Nicholas B Jennings,  Dariush Etemadmoghadam,  Luisa Capalbo,  Rodrigo O Jacamo,  Nuno Barbosa-Morais,  Xiao-Feng Le,  Australian Ovarian Cancer Study Group,  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 Jr
Affiliations

Affiliation

  • 1 Department of Experimental Therapeutics, M.D. Anderson Cancer Center, University of Texas, Houston, 77030, USA. [email protected]
PMID: 20708153 DOI: 10.1016/j.ccr.2010.06.018
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.

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