Cancer Research UK Beatson Institute, Glasgow, G61 1BD, UK.
Department of Oncology, NorLux Neuro-Oncology Laboratory, Luxembourg Institute of Health, L-1526, Luxembourg, Luxembourg.
Nat Commun. 2018 Apr 10;9(1):1368. doi: 10.1038/s41467-018-03777-w.
Formate overflow coupled to mitochondrial oxidative metabolism\ has been observed in cancer cell lines, but whether that takes place in the tumor microenvironment is not known. Here we report the observation of serine catabolism to formate in normal murine tissues, with a relative rate correlating with serine levels and the tissue oxidative state. Yet, serine catabolism to formate is increased in the transformed tissue of in vivo models of intestinal adenomas and mammary carcinomas. The increased serine catabolism to formate is associated with increased serum formate levels. Finally, we show that inhibition of formate production by genetic interference reduces cancer cell invasion and this phenotype can be rescued by exogenous formate. We conclude that increased formate overflow is a hallmark of oxidative cancers and that high formate levels promote invasion via a yet unknown mechanism.
已在癌细胞系中观察到与线粒体氧化代谢偶联的甲酸盐溢出，但在肿瘤微环境中是否存在这种情况尚不清楚。在这里，我们报告了在正常的鼠组织中观察到丝氨酸分解代谢为甲酸盐的情况，其相对速率与丝氨酸水平和组织氧化状态相关。然而，在体内结直肠腺瘤和乳腺癌模型的转化组织中，丝氨酸分解代谢为甲酸盐的速率增加。增加的丝氨酸分解代谢为甲酸盐与血清中甲酸盐水平升高有关。最后，我们表明通过遗传干扰抑制甲酸盐的产生会降低癌细胞的侵袭能力，而通过外源性甲酸盐可以挽救这种表型。我们得出结论，增加的甲酸盐溢出是氧化癌症的一个标志，而高甲酸盐水平通过未知机制促进侵袭。
