SIK2 is a centrosome kinase required for bipolar mitotic spindle formation that provides a potential target for therapy in ovarian cancer.
Enviado por Pablo Vivas-Mejia el
Título | SIK2 is a centrosome kinase required for bipolar mitotic spindle formation that provides a potential target for therapy in ovarian cancer. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Autores | Ahmed, AAshour, Lu, Z, Jennings, NB, Etemadmoghadam, D, Capalbo, L, Jacamo, RO, Barbosa-Morais, N, Le, X-F, Vivas-Mejia, P, Lopez-Berestein, G, Grandjean, G, Bartholomeusz, G, Liao, W, Andreeff, M, Bowtell, D, Glover, DM, Sood, AK, Bast, RC |
Corporate Authors | Australian Ovarian Cancer Study Group |
Journal | Cancer Cell |
Volume | 18 |
Issue | 2 |
Pagination | 109-21 |
Date Published | 2010 Aug 9 |
ISSN | 1878-3686 |
Palabras clave | Antineoplastic Agents, Phytogenic, Cell Cycle, Centrosome, Female, Humans, Ovarian Neoplasms, Paclitaxel, Phosphorylation, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-akt, RNA, Small Interfering, Spindle Apparatus, Transplantation, Heterologous |
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. |
DOI | 10.1016/j.ccr.2010.06.018 |
Alternate Journal | Cancer Cell |
PubMed ID | 20708153 |
PubMed Central ID | PMC3954541 |
Grant List | 11431 / / Cancer Research UK / United Kingdom 5P30CA016672-29 / CA / NCI NIH HHS / United States P30 CA016672 / CA / NCI NIH HHS / United States P50 CA083639 / CA / NCI NIH HHS / United States P50 CA083639 / CA / NCI NIH HHS / United States / / Cancer Research UK / United Kingdom |