Salt-Inducible Kinase 2 Couples Ovarian Cancer Cell Metabolism with Survival at the Adipocyte-Rich Metastatic Niche

Fabrizio Miranda, David Mannion, Shujuan Liu, Yiyan Zheng, Lingegowda S. Mangala, Clara Redondo, Sandra Herrero-Gonzalez, Ruoyan Xu, Charlotte Taylor, Donatien Fotso Chedom, Mohammad Karaminejadranjbar, Ashwag Albukhari, Dahai Jiang, Sunila Pradeep, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Eidarus Salah, Kamal R. Abdul Azeez, Jonathan M. Elkins, Leticia CampoKevin A. Myers, Daniel Klotz, Serena Bivona, Sunanda Dhar, Robert C. Bast, Hideyuki Saya, Hwan Geun Choi, Nathanael S. Gray, Roman Fischer, Benedikt M. Kessler, Christopher Yau, Anil K. Sood, Takeshi Motohara, Stefan Knapp, Ahmed Ashour Ahmed

研究成果: Article査読

74 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)273-289
ページ数17
ジャーナルCancer Cell
30
2
DOI
出版ステータスPublished - 2016 8 8

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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