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
  • 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.