CHTM1, a novel metabolic marker deregulated in human malignancies.
CHTM1, a novel metabolic marker deregulated in human malignancies.
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DOI：
10.1038/s41388-017-0051-9
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发表时间：
2018-04
期刊：
影响因子：
8
通讯作者：
Sheikh MS
中科院分区：
文献类型：
--
作者：
Babbar M;Huang Y;An J;Landas SK;Sheikh MS
需要更好地理解细胞代谢和肿瘤发生之间的联系。在这里，我们报告了一种新的蛋白质命名为卷曲螺旋阻碍肿瘤和代谢1（CHTM 1）的特性。我们发现CHTM 1与癌症和细胞代谢有关。CHTM 1定位于线粒体和细胞质，其在癌细胞中的缺乏导致线粒体耗氧量和ATP水平降低以及氧化应激，表明线粒体功能障碍。CHTM 1缺陷型癌细胞在葡萄糖/谷氨酰胺缺乏条件下生长不良，而表达外源性CHTM 1水平增加的细胞在类似条件下表现出增强的增殖和存活。CHTM 1缺乏还导致脂质代谢缺陷，导致脂肪酸积累，这解释了在葡萄糖/谷氨酰胺缺乏下CHTM 1缺乏细胞生长不良，因为营养缺乏增加了对脂质产生能量的依赖性。我们还证明，CHTM 1介导的作用，通过PKC，CREB和PGC-1 α信号轴，和细胞溶质积累的CHTM 1在营养剥夺过程中似乎是重要的，其对细胞信号事件的影响。此外，对来自71名乳腺癌和97名结肠癌患者的组织标本的分析显示，在代表这些恶性肿瘤的大多数肿瘤标本中，CHTM 1表达上调。总的来说，我们的发现是非常重要的，因为CHTM 1是一种新的代谢标志物，在有限的营养供应下对致瘤细胞的生长非常重要，因此，将细胞代谢和肿瘤发生联系起来。
A better understanding of the link between cellular metabolism and tumorigenesis is needed. Here, we report characterization of a novel protein named Coiled-coil Helix Tumor and Metabolism 1 (CHTM1). We have found that CHTM1 is associated with cancer and cellular metabolism. CHTM1 localizes to mitochondria and cytosol, and its deficiency in cancer cells results in decreased mitochondrial oxygen consumption and ATP levels as well as oxidative stress indicating mitochondrial dysfunction. CHTM1-deficient cancer cells display poor growth under glucose/glutamine-deprived conditions, whereas cells expressing increased levels of exogenous CHTM1 exhibit enhanced proliferation and survival under similar conditions. CHTM1 deficiency also leads to defects in lipid metabolism resulting in fatty acid accumulation, which explains poor growth of CHTM1-deficient cells under glucose/glutamine deprivation since nutrient deprivation increases dependency on lipids for energy generation. We also demonstrate that CHTM1 mediates its effect via the PKC, CREB and PGC-1alpha signaling axis, and cytosolic accumulation of CHTM1during nutrient deprivation appears to be important for its effect on cellular signaling events. Furthermore, analyses of tissue specimens from 71 breast and 97 colon cancer patients show CHTM1 expression to be upregulated in the majority of tumor specimens representing these malignancies. Collectively, our findings are highly significant because CHTM1 is a novel metabolic marker that is important for the growth of tumorigenic cells under limiting nutrient supplies and thus, links cellular metabolism and tumorigenesis.
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影响因子：
29
作者：
Pavlova NN;Thompson CB
通讯作者：
Thompson CB
DOI：
10.1016/j.neo.2015.08.005
发表时间：
2015-08
期刊：
Neoplasia (New York, N.Y.)
影响因子：
--
作者：
Simões RV;Serganova IS;Kruchevsky N;Leftin A;Shestov AA;Thaler HT;Sukenick G;Locasale JW;Blasberg RG;Koutcher JA;Ackerstaff E
通讯作者：
Ackerstaff E
影响因子：
64.8
作者：
Herzig, S;Hedrick, S;Montminy, M
通讯作者：
Montminy, M
影响因子：
7.1
作者：
Fernandez-Marcos, Pablo J.;Auwerx, Johan
通讯作者：
Auwerx, Johan
影响因子：
64.5
作者：
Puigserver, P;Wu, ZD;Spiegelman, BM
通讯作者：
Spiegelman, BM