Salt-Inducible Kinase 2 Couples Ovarian Cancer Cell Metabolism with Survival at the Adipocyte-Rich Metastatic Niche. Cancer Cell 2016 Aug 08;30(2):273-289
Date
08/02/2016Pubmed ID
27478041DOI
10.1016/j.ccell.2016.06.020Scopus ID
2-s2.0-84979768766 (requires institutional sign-in at Scopus site) 132 CitationsAbstract
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.
Author List
Miranda F, Mannion D, Liu S, Zheng Y, Mangala LS, Redondo C, Herrero-Gonzalez S, Xu R, Taylor C, Chedom DF, Carrami EM, Albukhari A, Jiang D, Pradeep S, Rodriguez-Aguayo C, Lopez-Berestein G, Salah E, Abdul Azeez KR, Elkins JM, Campo L, Myers KA, Klotz D, Bivona S, Dhar S, Bast RC Jr, Saya H, Choi HG, Gray NS, Fischer R, Kessler BM, Yau C, Sood AK, Motohara T, Knapp S, Ahmed AAAuthor
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AMP-Activated Protein KinasesAcetyl-CoA Carboxylase
Adipocytes
Animals
Female
Heterografts
Humans
Mice
Mice, Inbred C57BL
Mice, Nude
Neoplasm Metastasis
Oncogene Protein v-akt
Ovarian Neoplasms
Phosphatidylinositol 3-Kinases
Signal Transduction