Creatine-mediated crosstalk between adipocytes and cancer cells regulates obesity-driven breast cancer
Autor: | Christien B. Dykstra, Bozena Samborska, Caroline S. Jiang, Paul Cohen, Lawrence Kazak, Olivia A. Maguire, Janane F. Rahbani, Matthew G. Annis, Xiaojing Huang, Adriana Rosas-Villegas, Sarah K. Szwed, Rebecca G. Gelfer, Peter M. Siegel, François Marchildon, Ji Dung Luo, Raghavendra G. Mirmira, Daniel J. Kramer, Sarah E. Ackerman, Aarthi V. Maganti, Victor Ceballos, Lauren E. Turner, Sarah A. Tersey, Andrew J. Dannenberg, Thomas L. Carroll, Asal Hejazi |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Amidinotransferases Physiology Adipose tissue Breast Neoplasms Cell Communication Creatine Diet High-Fat Transcriptome 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Breast cancer Cell Line Tumor Coenzyme A Ligases Tumor Microenvironment Medicine Animals Humans Obesity RNA Small Interfering Molecular Biology Mice Knockout Tumor microenvironment business.industry Membrane Transport Proteins Cell Biology medicine.disease 3. Good health Mice Inbred C57BL Crosstalk (biology) 030104 developmental biology chemistry Adipose Tissue Tumor progression Cancer cell Cancer research Female RNA Interference business 030217 neurology & neurosurgery |
Zdroj: | Cell metabolism. 33(3) |
ISSN: | 1932-7420 |
Popis: | Obesity is a major risk factor for adverse outcomes in breast cancer; however, the underlying molecular mechanisms have not been elucidated. To investigate the role of crosstalk between mammary adipocytes and neoplastic cells in the tumor microenvironment (TME), we performed transcriptomic analysis of cancer cells and adjacent adipose tissue in a murine model of obesity-accelerated breast cancer and identified glycine amidinotransferase (Gatm) in adipocytes and Acsbg1 in cancer cells as required for obesity-driven tumor progression. Gatm is the rate-limiting enzyme in creatine biosynthesis, and deletion in adipocytes attenuated obesity-driven tumor growth. Similarly, genetic inhibition of creatine import into cancer cells reduced tumor growth in obesity. In parallel, breast cancer cells in obese animals upregulated the fatty acyl-CoA synthetase Acsbg1 to promote creatine-dependent tumor progression. These findings reveal key nodes in the crosstalk between adipocytes and cancer cells in the TME necessary for obesity-driven breast cancer progression. |
Databáze: | OpenAIRE |
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