The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type.
The metabolic profile of tumors depends on both the responsible genetic lesion and tissue type.
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DOI：
10.1016/j.cmet.2011.12.015
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发表时间：
2012-02-08
期刊：
影响因子：
29
通讯作者：
Bishop JM
中科院分区：
文献类型：
--
作者：
Yuneva MO;Fan TW;Allen TD;Higashi RM;Ferraris DV;Tsukamoto T;Matés JM;Alonso FJ;Wang C;Seo Y;Chen X;Bishop JM
肿瘤代谢的改变已被认为是抗癌治疗的靶点。然而，不同的肿瘤起始病变和体内肿瘤代谢异常之间的关系尚未得到解决。我们报道MYC诱导的小鼠肝肿瘤显著增加葡萄糖和谷氨酰胺催化剂，而MET诱导的肝肿瘤使用葡萄糖产生谷氨酰胺。MYC诱导的肝肿瘤中谷氨酰胺催化剂的增加与谷氨酰胺合成酶（Glul）水平的降低以及谷氨酰胺酶从Gls2转换为Gls1相关。与肝肿瘤相比，MYC诱导的肺肿瘤显示Glul和Gls1表达增加并积累谷氨酰胺。我们还表明，Gls1的抑制杀死过表达MYC和分解代谢谷氨酰胺的细胞。我们的研究结果表明，肿瘤的代谢谱可能取决于基因型和起源组织，并对靶向肿瘤代谢的治疗设计产生影响。
The altered metabolism of tumors has been considered a target for anti-cancer therapy. However, the relationship between distinct tumor-initiating lesions and anomalies of tumor metabolism in vivo has not been addressed. We report that MYC-induced mouse liver tumors significantly increase both glucose and glutamine catabolism, whereas MET-induced liver tumors use glucose to produce glutamine. Increased glutamine catabolism in MYC-induced liver tumors is associated with decreased levels of glutamine synthetase (Glul) and the switch from Gls2 to Gls1 glutaminase. In contrast to liver tumors, MYC-induced lung tumors display increased expression of both Glul and Gls1 and accumulate glutamine. We also show that inhibition of Gls1 kills cells that over-express MYC and catabolize glutamine. Our results suggest that the metabolic profiles of tumors are likely to depend on both the genotype and tissue of origin and have implications regarding the design of therapies targeting tumor metabolism.
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影响因子：
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