| Autor: |
Jonathan M. Elkins, Sunila Pradeep, Anil K. Sood, Nathanael S. Gray, Stefan Knapp, Gabriel Lopez-Berestein, Leticia Campo, Robert C. Bast, Cristian Rodriguez-Aguayo, Fabrizio Miranda, Mohammad KaramiNejadRanjbar, Ashwag Albukhari, Sunanda Dhar, Benedikt M. Kessler, Shujuan Liu, Lingegowda S. Mangala, Serena Bivona, Donatien Fotso Chedom, Clara Redondo, Takeshi Motohara, Roman Fischer, Christopher Yau, Charlotte Taylor, Eidarus Salah, Hideyuki Saya, Hwan Geun Choi, Yiyan Zheng, David Mannion, Ruoyan Xu, Dahai Jiang, Sandra Herrero-Gonzalez, Ahmed Ashour Ahmed, Daniel Klotz, Kamal R. Abdul Azeez, Kevin A. Myers |
| Rok vydání: |
2014 |
| Předmět: |
|
| Zdroj: |
Cancer cell. 30(2) |
| ISSN: |
1878-3686 |
| Popis: |
The adipocyte-rich microenvironment forms a niche for ovarian cancer metastasis, but the mechanisms driving this process are incompletely understood. Here we show that salt-inducible kinase 2 (SIK2) is overexpressed in adipocyte-rich metastatic deposits compared with ovarian primary lesions. Overexpression of SIK2 in ovarian cancer cells promotes abdominal metastasis while SIK2 depletion prevents metastasis in vivo. Importantly, adipocytes induce calcium-dependent activation and autophosphorylation of SIK2. Activated SIK2 plays a dual role in augmenting AMPK-induced phosphorylation of acetyl-CoA carboxylase and in activating the PI3K/AKT pathway through p85α-S154 phosphorylation. These findings identify SIK2 at the apex of the adipocyte-induced signaling cascades in cancer cells and make a compelling case for targeting SIK2 for therapy in ovarian cancer. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
