Creatine-mediated crosstalk between adipocytes and cancer cells regulates obesity-driven breast cancer.
Creatine-mediated crosstalk between adipocytes and cancer cells regulates obesity-driven breast cancer.
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DOI：
10.1016/j.cmet.2021.01.018
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发表时间：
2021-03-02
期刊：
影响因子：
29
通讯作者：
Cohen P
中科院分区：
文献类型：
--
作者：
Maguire OA;Ackerman SE;Szwed SK;Maganti AV;Marchildon F;Huang X;Kramer DJ;Rosas-Villegas A;Gelfer RG;Turner LE;Ceballos V;Hejazi A;Samborska B;Rahbani JF;Dykstra CB;Annis MG;Luo JD;Carroll TS;Jiang CS;Dannenberg AJ;Siegel PM;Tersey SA;Mirmira RG;Kazak L;Cohen P
肥胖是乳腺癌不良结局的主要危险因素；然而，其潜在的分子机制尚未阐明。为了研究乳腺脂肪细胞和肿瘤细胞之间的串扰在肿瘤微环境(TME)中的作用，我们对肥胖加速乳腺癌小鼠模型中的癌细胞和邻近脂肪组织进行了转录转录分析，并确定了脂肪细胞中的甘氨酸氨基转移酶(GATM)和癌细胞中的Acsbg1是肥胖驱动的肿瘤进展所必需的。GATM是肌酸生物合成的限速酶，脂肪细胞中的缺失可以抑制肥胖驱动的肿瘤生长。同样，抑制肌酸进入癌细胞的基因减少了肥胖患者的肿瘤生长。同时，肥胖动物的乳腺癌细胞上调脂肪酰辅酶A合成酶Acsbg1，以促进肌酸依赖的肿瘤进展。这些发现揭示了脂肪细胞和癌细胞之间在TME中的关键节点，TME是肥胖驱动的乳腺癌进展所必需的。肥胖是乳腺癌不良后果的主要风险因素。Maguire，Ackerman等人。揭示Gatm和Acsbg1是肥胖驱动的乳腺癌进展的分子调节因子。他们进一步表明，在肥胖中，肌酸是脂肪细胞和乳腺肿瘤之间相互作用的关键代谢物。
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. Obesity is a major risk factor for adverse outcomes in breast cancer. Maguire, Ackerman et al. reveal Gatm and Acsbg1 as molecular regulators of obesity-driven breast cancer progression. They further show that in obesity creatine is a key metabolite in the crosstalk between adipocytes and breast tumors.
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影响因子：
4.2
作者：
Morris, Sidney M., Jr.
通讯作者：
Morris, Sidney M., Jr.
影响因子：
14.9
作者：
López-Ibáñez J;Pazos F;Chagoyen M
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细胞外代谢能量可以促进癌症的进展。
影响因子：
64.5
作者：
Loo JM;Scherl A;Nguyen A;Man FY;Weinberg E;Zeng Z;Saltz L;Paty PB;Tavazoie SF
通讯作者：
Tavazoie SF
影响因子：
8.9
作者：
Grevengoed TJ;Klett EL;Coleman RA
通讯作者：
Coleman RA
影响因子：
3.5
作者：
Lopes-Marques, Monica;Machado, Andre M.;Castro, L. Filipe C.
通讯作者：
Castro, L. Filipe C.