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.
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DOI：
10.1016/j.ccr.2010.06.018
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发表时间：
2010-08-09
期刊：
影响因子：
50.3
通讯作者：
Bast RC Jr
中科院分区：
文献类型：
--
作者：
Ahmed AA;Lu Z;Jennings NB;Etemadmoghadam D;Capalbo L;Jacamo RO;Barbosa-Morais N;Le XF;Australian Ovarian Cancer Study Group;Vivas-Mejia P;Lopez-Berestein G;Grandjean G;Bartholomeusz G;Liao W;Andreeff M;Bowtell D;Glover DM;Sood AK;Bast RC Jr
有丝分裂调节因子已成功地被靶向增强对紫杉烷化疗的反应。在这里，我们发现盐诱导蛋白2(SIK2)定位于中心体，在有丝分裂的启动中起关键作用，并通过S2392的磷酸化调节中心体连接蛋白C-NAP1的定位。干扰已知的SIK2抑制剂PKA诱导SIK2依赖的中心体分裂在间期，而SIK2缺失阻止有丝分裂中的中心体分离，在培养和异种移植中使卵巢癌对紫杉醇增敏。SIK2的缺失也延迟了G1/S的转变，降低了AKT的磷酸化。在高级别浆液性卵巢癌患者中，SIK2的高表达与患者的低生存率显著相关。这些数据表明，SIK2可能是卵巢癌治疗的靶点。
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. These data identify SIK2 as a plausible target for therapy in ovarian cancers.
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DOI：
10.1093/jnci/83.11.757
发表时间：
1991-06-05
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
MONKS, A;SCUDIERO, D;BOYD, M
通讯作者：
BOYD, M
影响因子：
10.3
作者：
Martin, Miguel;Rodriguez-Lescure, Alvaro;Manuel Lopez-Vega, Jose
通讯作者：
Manuel Lopez-Vega, Jose
影响因子：
5.4
作者：
Katoh, Yoshiko;Takemori, Hiroshi;Okamoto, Mitsuhiro
通讯作者：
Okamoto, Mitsuhiro
影响因子：
50.3
作者：
Ahmed AA;Mills AD;Ibrahim AE;Temple J;Blenkiron C;Vias M;Massie CE;Iyer NG;McGeoch A;Crawford R;Nicke B;Downward J;Swanton C;Bell SD;Earl HM;Laskey RA;Caldas C;Brenton JD
通讯作者：
Brenton JD
影响因子：
11.2
作者：
O'Reilly, KE;Rojo, F;Rosen, N
通讯作者：
Rosen, N