Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer.
Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer.
复制标题
DOI：
10.1016/j.chembiol.2011.05.009
复制
发表时间：
2011-07-29
影响因子：
--
通讯作者：
Cravatt BF
中科院分区：
文献类型：
--
作者：
Nomura DK;Lombardi DP;Chang JW;Niessen S;Ward AM;Long JZ;Hoover HH;Cravatt BF
癌细胞将脂肪生成和脂肪分解结合起来，产生支持恶性肿瘤的脂肪酸网络。单酰基甘油脂肪酶（MAGL）通过将甘油单酯（包括内源性大麻素2-花生四烯酰甘油（2-AG））转化为游离脂肪酸在该过程中起主要作用。在这里，我们发现MAGL在雄激素非依赖性与雄激素依赖性人前列腺癌细胞系中升高，并且这种酶的药理学或RNA干扰破坏损害前列腺癌的侵袭性。这些影响被部分逆转的治疗脂肪酸或大麻素受体-1（CB 1）拮抗剂，并完全逆转的共同治疗与这两种药物。我们进一步表明，MAGL是与上皮细胞向间充质细胞转化和癌细胞干细胞样特性相关的基因特征的一部分，支持这种酶在促肿瘤发生代谢中的作用，对于前列腺癌，涉及内源性大麻素和脂肪酸途径的双重控制。
Cancer cells couple heightened lipogenesis with lipolysis to produce fatty acid networks that support malignancy. Monoacylglycerol lipase (MAGL) plays a principal role in this process by converting monoglycerides, including the endocannabinoid 2-arachidonoylglycerol (2-AG), to free fatty acids. Here, we show that MAGL is elevated in androgen-independent versus androgen-dependent human prostate cancer cell lines, and that pharmacological or RNA-interference disruption of this enzyme impairs prostate cancer aggressiveness. These effects were partially reversed by treatment with fatty acids or a cannabinoid receptor-1 (CB1) antagonist, and fully reversed by co-treatment with both agents. We further show that MAGL is part of a gene signature correlated with epithelial-to-mesenchymal transition and the stem-like properties of cancer cells, supporting a role for this enzyme in pro-tumorigenic metabolism that, for prostate cancer, involves the dual control of endocannabinoid and fatty acid pathways.
登录
查看更多内容
大麻素通过抑制 Akt 来减少 ErbB2 驱动的乳腺癌进展。
影响因子：
37.3
作者：
Caffarel, Maria M.;Andradas, Clara;Mira, Emilia;Perez-Gomez, Eduardo;Cerutti, Camilla;Moreno-Bueno, Gema;Flores, Juana M.;Garcia-Real, Isabel;Palacios, Jose;Manes, Santos;Guzman, Manuel;Sanchez, Cristina
通讯作者：
Sanchez, Cristina
影响因子：
4
作者：
Joyce, Tobias;Cantarella, Daniela;Pintzas, Alexander
通讯作者：
Pintzas, Alexander
影响因子：
--
作者：
Chang JW;Nomura DK;Cravatt BF
通讯作者：
Cravatt BF
影响因子：
6.4
作者：
Endsley, Michael P.;Thill, Rebecca;Nithipatikom, Kasem
通讯作者：
Nithipatikom, Kasem
影响因子：
3.6
作者：
Chanda, Pranab K.;Gao, Ying;Samad, Tarek A.
通讯作者：
Samad, Tarek A.