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Salt-Inducible Kinase 2 Couples Ovarian Cancer Cell Metabolism with Survival at the Adipocyte-Rich Metastatic Niche. Cancer Cell 2016 08 08;30(2):273-289

Date

08/02/2016

Pubmed ID

27478041

DOI

10.1016/j.ccell.2016.06.020

Scopus ID

2-s2.0-84979768766   66 Citations

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.

Author List

Miranda F, Mannion D, Liu S, Zheng Y, Mangala LS, Redondo C, Herrero-Gonzalez S, Xu R, Taylor C, Chedom DF, Karaminejadranjbar M, 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 AA

Author

Sunila Pradeep PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

AMP-Activated Protein Kinases
Acetyl-CoA Carboxylase
Adipocytes
Animals
Female
Heterografts
Humans
Mice
Mice, Inbred C57BL
Mice, Nude
Neoplasm Metastasis
Oncogene Protein v-akt
Ovarian Neoplasms
Phosphatidylinositol 3-Kinases
Protein-Serine-Threonine Kinases
Signal Transduction
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a