代谢重编程是肿瘤细胞的十大特征之一。前期研究中，我们揭示了营养压力条件下丝氨酸代谢通路的激活（Sun L et al., 2015, Cell research）。在此基础上，本项目将进一步研究肿瘤低氧微环境对一碳代谢的调控及其机制。一碳代谢和丝氨酸代谢紧密相连，后者可以通过形成丝氨酸、甘氨酸等参与一碳代谢循环，进而为肿瘤细胞提供核苷酸、蛋白质、脂质及维持氧化还原稳态的辅因子等生物大分子。我们尚未发表的数据表明低氧条件下，多种一碳代谢酶的表达发生改变，但是低氧调节一碳代谢的机制和生物学意义并不十分清楚。因此，本项目将在分子、细胞、动物及临床样品等不同层次，来研究低氧对一碳代谢异常的调节，并通过寻找其上游的调控分子及其下游的靶标, 来解析低氧微环境调控一碳代谢的机制及其临床意义。我们的研究目标是揭示一碳代谢异常影响肿瘤发病的新机制，并探索通过干预一碳代谢相关关键因子从而靶向治疗肿瘤的新方法。

One of the emerging hallmarks of cancer cells has been the deregulated cellular metabolism, which is the adaptive response when cancer cells were encountered with tumor microenvironment stress such as nutrient deprivation and hypoxia. We have documented previously that serine synthesis pathway (SSP) is activated under nutrient stress conditions (Sun L et al., 2015, Cell research). SSP is known to be involved in one carbon metabolism, which provides nucleotides, proteins, lipids, cofactors of redox homeostasis and other building blocks for metabolic reprogramming, through biosynthesis and interconversion between serine and glycine. Thus, we propose here to study the alteration of one carbon metabolism under hypoxic conditions and its effects on cancer progression. Our unpublished preliminary observations showed that many one carbon metabolism enzymes are altered under hypoxic conditions, but the regulatory mechanism and biological significance are unknown. In this study, we will further study how hypoxia regulates one carbon metabolism and explore the upstream mechanism and downstream significance. With the purpose to uncover new mechanism of carcinogenesis, we will also explore to target the deregulated one carbon metabolism related key factors for cancer therapy.