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科学家揭示肥胖如何影响乳腺癌恶化
作者:小柯机器人 发布时间:2021/2/18 14:52:32

美国洛克菲勒大学Paul Cohen小组发现,肌酸介导的脂肪细胞与癌细胞之间的交流调节肥胖引起的乳腺癌。该项研究成果于2021年2月16日在线发表在《细胞—代谢》杂志上。

为了研究乳腺脂肪细胞和肿瘤细胞在肿瘤微环境(TME)中的交流作用,研究在肥胖加速型乳腺癌小鼠模型中对癌细胞和邻近脂肪组织进行了转录组分析,并鉴定了脂肪细胞中甘氨酸脒基转移酶(Gatm)和癌细胞中的Acsbg1。Gatm是肌酸生物合成中的限速酶,而脂肪细胞中的缺失减弱了肥胖引起的肿瘤生长。类似地,对肌酸输入癌细胞的遗传抑制降低了肥胖症中的肿瘤生长。

同时,肥胖动物中的乳腺癌细胞上调了脂肪酰基辅酶A合成酶Acsbg1,从而促进了肌酸依赖性肿瘤的进展。这些发现揭示了肥胖引起的乳腺癌进展肿瘤微环境中脂肪细胞与癌细胞之间交流的关键节点。

研究人员介绍,肥胖是乳腺癌不良后果的主要危险因素。然而,尚未阐明潜在的分子机制。

附:英文原文

Title: Creatine-mediated crosstalk between adipocytes and cancer cells regulates obesity-driven breast cancer

Author: Olivia A. Maguire, Sarah E. Ackerman, Sarah K. Szwed, Aarthi V. Maganti, Franois Marchildon, Xiaojing Huang, Daniel J. Kramer, Adriana Rosas-Villegas, Rebecca G. Gelfer, Lauren E. Turner, Victor Ceballos, Asal Hejazi, Bozena Samborska, Janane F. Rahbani, Christien B. Dykstra, Matthew G. Annis, Ji-Dung Luo, Thomas S. Carroll, Caroline S. Jiang, Andrew J. Dannenberg, Peter M. Siegel, Sarah A. Tersey, Raghavendra G. Mirmira, Lawrence Kazak, Paul Cohen

Issue&Volume: 2021-02-16

Abstract: Obesity is a major risk factor for adverse outcomes in breast cancer; however, theunderlying molecular mechanisms have not been elucidated. To investigate the roleof crosstalk between mammary adipocytes and neoplastic cells in the tumor microenvironment(TME), we performed transcriptomic analysis of cancer cells and adjacent adipose tissuein 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 tumorprogression. Gatm is the rate-limiting enzyme in creatine biosynthesis, and deletionin adipocytes attenuated obesity-driven tumor growth. Similarly, genetic inhibitionof creatine import into cancer cells reduced tumor growth in obesity. In parallel,breast cancer cells in obese animals upregulated the fatty acyl-CoA synthetase Acsbg1to promote creatine-dependent tumor progression. These findings reveal key nodes inthe crosstalk between adipocytes and cancer cells in the TME necessary for obesity-drivenbreast cancer progression.

DOI: 10.1016/j.cmet.2021.01.018

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00056-5

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx