| Literature DB >> 33596409 |
Olivia A Maguire1, Sarah E Ackerman2, Sarah K Szwed1, Aarthi V Maganti3, François Marchildon3, Xiaojing Huang4, Daniel J Kramer1, Adriana Rosas-Villegas3, Rebecca G Gelfer5, Lauren E Turner3, Victor Ceballos3, Asal Hejazi3, Bozena Samborska6, Janane F Rahbani6, Christien B Dykstra6, Matthew G Annis7, Ji-Dung Luo8, Thomas S Carroll8, Caroline S Jiang9, Andrew J Dannenberg10, Peter M Siegel6, Sarah A Tersey11, Raghavendra G Mirmira11, Lawrence Kazak6, Paul Cohen12.
Abstract
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.Entities:
Keywords: Acsbg1; Gatm; breast cancer; creatine; hypoxia; obesity
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Year: 2021 PMID： 33596409 PMCID： PMC7954401 DOI： 10.1016/j.cmet.2021.01.018
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287