期刊
CANCER CELL
卷 18, 期 2, 页码 109-121出版社
CELL PRESS
DOI: 10.1016/j.ccr.2010.06.018
关键词
-
资金
- Cancer Research UK
- University of Cambridge
- Zarrow Foundation
- Ovarian Cancer Research Fund
- University of Texas M D Anderson Cancer Center [P50 CA083639]
- Addenbrooke's Charitable Trust
- Cancer Council Victoria
- Queensland Cancer Fund
- Cancer Council New South Wales
- Cancer Council South Australia
- Cancer Foundation of Western Australia
- Cancer Council Tasmania
- National Health and Medical Research Council of Australia (NHMRC)
- NCI [5P30CA016672-29]
- Cancer Research UK [11431] Funding Source: researchfish
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据