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 CHTM1 during 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.

中文翻译：

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CHTM1，一种在人类恶性肿瘤中失控的新型代谢标记物。

需要更好地了解细胞代谢与肿瘤发生之间的联系。在这里，我们报道了一种新型蛋白质，称为卷曲螺旋螺旋肿瘤和新陈代谢1（CHTM1）的表征。我们发现CHTM1与癌症和细胞代谢有关。CHTM1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含量降低，氧化应激表明线粒体功能异常。缺乏CHTM1的癌细胞在缺乏葡萄糖/谷氨酰胺的条件下表现出不良的生长，而表达增加水平的外源CHTM1的细胞在相似条件下表现出增强的增殖和存活率。CHTM1缺乏症还会导致脂质代谢缺陷，从而导致脂肪酸蓄积，这解释了缺乏葡萄糖/谷氨酰胺的情况下缺乏CHTM1的细胞的不良生长，因为营养物质的缺乏增加了对脂质产生能量的依赖性。我们还证明了CHTM1通过PKC，CREB和PGC-1alpha信号转导轴介导其作用，并且营养物剥夺期间CHTM1的胞质积累似乎对其作用对细胞信号转导事件很重要。此外，对来自71位乳腺癌和97位结肠癌患者的组织标本的分析表明，在代表这些恶性肿瘤的大多数肿瘤标本中，CHTM1表达均被上调。总的来说，我们的发现非常重要，因为CHTM1是一种新型的代谢标志物，在限制营养供应的情况下对于致瘤细胞的生长很重要，因此将细胞代谢与肿瘤发生联系在一起。