| Literature DB >> 27478041 |
Fabrizio Miranda1, David Mannion1, Shujuan Liu1, Yiyan Zheng1, Lingegowda S Mangala2, Clara Redondo3, Sandra Herrero-Gonzalez1, Ruoyan Xu1, Charlotte Taylor1, Donatien Fotso Chedom1, Mohammad Karaminejadranjbar1, Ashwag Albukhari4, Dahai Jiang2, Sunila Pradeep5, Cristian Rodriguez-Aguayo6, Gabriel Lopez-Berestein6, Eidarus Salah7, Kamal R Abdul Azeez7, Jonathan M Elkins7, Leticia Campo8, Kevin A Myers8, Daniel Klotz1, Serena Bivona1, Sunanda Dhar9, Robert C Bast10, Hideyuki Saya11, Hwan Geun Choi12, Nathanael S Gray12, Roman Fischer13, Benedikt M Kessler13, Christopher Yau14, Anil K Sood2, Takeshi Motohara15, Stefan Knapp16, Ahmed Ashour Ahmed17.
Abstract
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. CrownEntities:
Mesh：
Substances：
Year: 2016 PMID： 27478041 DOI： 10.1016/j.ccell.2016.06.020
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743