Metabolic Adaptation to Nutritional Stress in Human Colorectal Cancer.
Metabolic Adaptation to Nutritional Stress in Human Colorectal Cancer.
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DOI：
10.1038/srep38415
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发表时间：
2016-12-07
影响因子：
4.6
通讯作者：
Ishii H
中科院分区：
文献类型：
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作者：
Miyo M;Konno M;Nishida N;Sueda T;Noguchi K;Matsui H;Colvin H;Kawamoto K;Koseki J;Haraguchi N;Nishimura J;Hata T;Gotoh N;Matsuda F;Satoh T;Mizushima T;Shimizu H;Doki Y;Mori M;Ishii H
肿瘤细胞对它们的微环境做出反应，包括缺氧和营养不良，并适应它们的代谢以生存和生长。一些癌基因通过调节相关酶或转运蛋白与癌症代谢相关。然而，代谢的重要性和癌基因在结直肠癌中精确的代谢作用仍不清楚。我们发现结直肠癌细胞在葡萄糖耗尽的条件下存活，它们对这种条件的抵抗取决于基因组改变，而不仅仅是KRAS突变。代谢组学分析表明，这些细胞在这种条件下保持三羧酸循环活性和ATP产生。此外，我们确定了GLUD1和SLC25A13在营养应激中的关键作用。GLUD1和SLC25A13与结直肠癌的侵袭性和不良预后相关。总之，GLUD1和SLC25A13可以作为治疗在营养不良微环境中生存的难治性结直肠癌的新靶点。
Tumor cells respond to their microenvironment, which can include hypoxia and malnutrition, and adapt their metabolism to survive and grow. Some oncogenes are associated with cancer metabolism via regulation of the related enzymes or transporters. However, the importance of metabolism and precise metabolic effects of oncogenes in colorectal cancer remain unclear. We found that colorectal cancer cells survived under the condition of glucose depletion, and their resistance to such conditions depended on genomic alterations rather than on KRAS mutation alone. Metabolomic analysis demonstrated that those cells maintained tricarboxylic acid cycle activity and ATP production under such conditions. Furthermore, we identified pivotal roles of GLUD1 and SLC25A13 in nutritional stress. GLUD1 and SLC25A13 were associated with tumor aggressiveness and poorer prognosis of colorectal cancer. In conclusion, GLUD1 and SLC25A13 may serve as new targets in treating refractory colorectal cancer which survive in malnutritional microenvironments.
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影响因子：
8.8
作者：
Miyo M;Yamamoto H;Konno M;Colvin H;Nishida N;Koseki J;Kawamoto K;Ogawa H;Hamabe A;Uemura M;Nishimura J;Hata T;Takemasa I;Mizushima T;Doki Y;Mori M;Ishii H
通讯作者：
Ishii H
影响因子：
9.9
作者：
Gaglio, Daniela;Metallo, Christian M.;Chiaradonna, Ferdinando
通讯作者：
Chiaradonna, Ferdinando
影响因子：
3.5
作者：
Dasu, A;Toma-Dasu, I;Karlsson, M
通讯作者：
Karlsson, M
影响因子：
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作者：
Ohashi, Yoshiaki;Hirayama, Akiyoshi;Soga, Tomoyoshi
通讯作者：
Soga, Tomoyoshi
p53和苹果酶的相互调节调节新陈代谢和衰老。
影响因子：
64.8
作者：
通讯作者：
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