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Salt-Inducible Kinase 2 Couples Ovarian Cancer Cell Metabolism with Survival at the Adipocyte-Rich Metastatic Niche.
Miranda, Fabrizio; Mannion, David; Liu, Shujuan; Zheng, Yiyan; Mangala, Lingegowda S; Redondo, Clara; Herrero-Gonzalez, Sandra; Xu, Ruoyan; Taylor, Charlotte; Chedom, Donatien Fotso; Carrami, Eli M; Albukhari, Ashwag; Jiang, Dahai; Pradeep, Sunila; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Salah, Eidarus; Abdul Azeez, Kamal R; Elkins, Jonathan M; Campo, Leticia; Myers, Kevin A; Klotz, Daniel; Bivona, Serena; Dhar, Sunanda; Bast, Robert C; Saya, Hideyuki; Choi, Hwan Geun; Gray, Nathanael S; Fischer, Roman; Kessler, Benedikt M; Yau, Christopher; Sood, Anil K; Motohara, Takeshi; Knapp, Stefan; Ahmed, Ahmed Ashour.
Afiliação
  • Miranda F; Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
  • Mannion D; Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
  • Liu S; Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
  • Zheng Y; Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
  • Mangala LS; Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA; Center for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
  • Redondo C; Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK; Structural Genomics Consortium, Nuff
  • Herrero-Gonzalez S; Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
  • Xu R; Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
  • Taylor C; Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
  • Chedom DF; Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
  • Carrami EM; Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
  • Albukhari A; Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK; Biochemistry Department, Faculty of
  • Jiang D; Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA; Center for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
  • Pradeep S; Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
  • Rodriguez-Aguayo C; Center for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA; Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
  • Lopez-Berestein G; Center for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA; Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
  • Salah E; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Abdul Azeez KR; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Elkins JM; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
  • Campo L; Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.
  • Myers KA; Department of Oncology, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.
  • Klotz D; Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
  • Bivona S; Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK.
  • Dhar S; Department of Histopathology, Oxford University Hospitals, Oxford OX3 9DU, UK.
  • Bast RC; Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
  • Saya H; Division of Gene Regulation, Institute for Advanced Medical Research, School of Medicine, Keio University, Tokyo 160-8582, Japan.
  • Choi HG; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA.
  • Gray NS; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02215, USA.
  • Fischer R; Nuffield Department of Medicine, Target Discovery Institute, University of Oxford, Oxford OX3 7FZ, UK.
  • Kessler BM; Nuffield Department of Medicine, Target Discovery Institute, University of Oxford, Oxford OX3 7FZ, UK.
  • Yau C; Wellcome Trust Centre for Human Genetics, NIHR Biomedical Research Centre, Roosevelt Drive, Oxford OX3 7BN, UK; Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK.
  • Sood AK; Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA; Center for RNAi and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
  • Motohara T; Department of Obstetrics and Gynecology, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
  • Knapp S; Structural Genomics Consortium, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK; Nuffield Department of Medicine, Target Discovery Institute, University of Oxford, Oxford OX3 7FZ, UK; Goethe-University Frankfurt, Institute for Pharmaceutic
  • Ahmed AA; Ovarian Cancer Cell Laboratory, Weatherall Institute of Molecular Medicine, University of Oxford, Headington, Oxford OX3 9DS, UK; Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, UK. Electronic address: ahmed.ahmed@obs-
Cancer Cell ; 30(2): 273-289, 2016 08 08.
Article em En | MEDLINE | ID: mdl-27478041
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2016 Tipo de documento: Article