Dihydropyrimidine accumulation is required for the epithelial-mesenchymal transition.
Dihydropyrimidine accumulation is required for the epithelial-mesenchymal transition.
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DOI：
10.1016/j.cell.2014.07.032
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发表时间：
2014-08-28
期刊：
影响因子：
64.5
通讯作者：
Sabatini DM
中科院分区：
文献类型：
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作者：
Shaul YD;Freinkman E;Comb WC;Cantor JR;Tam WL;Thiru P;Kim D;Kanarek N;Pacold ME;Chen WW;Bierie B;Possemato R;Reinhardt F;Weinberg RA;Yaffe MB;Sabatini DM
越来越多的人认识到致癌转化改变细胞代谢以促进细胞增殖，但对促进癌细胞侵袭性的代谢变化知之甚少。在这里，我们分析了癌细胞系中的代谢基因表达，发现一组表达间充质标志物的高级别癌细胞系共享一个独特的44基因签名，称为“间充质代谢签名”（MMS）。基于FACS的shRNA筛选确定了几个MMS基因对上皮-间充质转化（EMT）而不是细胞增殖是必需的。二氢嘧啶脱氢酶（DPYD），一种嘧啶降解酶，在EMT诱导后高度表达，并且是细胞在体外获得间充质特性和致瘤细胞外渗到小鼠肺中所必需的。DPYD的这种作用是通过其催化活性和酶产物二氢嘧啶介导的。因此，我们确定了EMT所必需的代谢过程，EMT是一个与获得转移性和侵袭性癌细胞性状相关的程序。
It is increasingly appreciated that oncogenic transformation alters cellular metabolism to facilitate cell proliferation, but less is known about the metabolic changes that promote cancer cell aggressiveness. Here, we analyzed metabolic gene expression in cancer cell lines and found that a set of high-grade carcinoma lines expressing mesenchymal markers shared a unique 44-gene signature, designated the “mesenchymal metabolic signature” (MMS). A FACS-based shRNA screen identified several MMS genes as essential for the epithelial-mesenchymal transition (EMT) but not for cell proliferation. Dihydropyrimidine dehydrogenase (DPYD), a pyrimidine-degrading enzyme, was highly expressed upon EMT induction and was necessary for cells to acquire mesenchymal characteristics in vitro and for tumorigenic cells to extravasate into the mouse lung. This role of DPYD was mediated through its catalytic activity and enzymatic products, the dihydropyrimidines. Thus, we identify metabolic processes essential for the EMT, a program associated with the acquisition of metastatic and aggressive cancer cell traits.
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影响因子：
46.9
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影响因子：
64.5
作者：
Nomura DK;Long JZ;Niessen S;Hoover HS;Ng SW;Cravatt BF
通讯作者：
Cravatt BF
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影响因子：
64.8
作者：
通讯作者：
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