Cell research：cMyc调节肿瘤细胞代谢新机制

    近日，中国科技大学研究人员在国际学术期刊Cell research 在线发表了他们的最新研究进展，他们发现在营养缺乏状态下，cMyc能够激活丝氨酸合成途径维持癌细胞存活促进细胞增殖，这表明在肿瘤细胞代谢转换过程中cMyc发挥了重要作用。

    众所周知，癌细胞为维持自身存活以及快速增殖会进行代谢重编程过程，但是癌基因如何在各种应激条件下实现代谢转变过程仍不清楚。研究人员发现癌细胞在缺少葡萄糖或谷氨酰胺这两种主要营养来源的情况下，能够显著激活丝氨酸合成途径(SSP)，同时伴随cMYC表达增加。

    研究人员进一步证实，cMYC能够在转录水平上调丝氨酸合成途径中几种关键酶的表达实现对丝氨酸合成途径的激活。SSP途径激活会促进谷胱甘肽合成，细胞周期进展以及核酸合成，通过这些过程维持癌细胞在营养缺乏状态下的细胞存活并促进癌细胞增殖。研究人员还发现SSP途径的最后限速酶，磷酸丝氨酸磷酸化酶(PSPH)，对于cMyc驱动的癌症进程非常重要，同时PSPH的异常表达与肝细胞癌(HCC)病人的死亡率高度相关，这表明

     cMyc介导的SSP途径激活与癌症的发展具有密切联系。

    总的来说，这项研究证明了cMyc的异常表达能够导致丝氨酸合成途径的激活，这一过程在癌细胞代谢转换过程中具有重要促进作用，对于维持营养匮乏状态下癌细胞的正常存活和细胞增殖，促进癌症进展，具有重要作用。

    原文链接：cMyc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrientdeprivation conditions.

Cancer cells are known to undergo metabolic reprogramming to sustain survival and rapid proliferation, however, it remains to be fully elucidated how oncogenic lesions coordinate the metabolic switch under various stressed conditions. Here we show that deprivation of glucose or glutamine, two major nutrition sources for cancer cells, dramatically activated serine biosynthesis pathway (SSP) that was accompanied by elevated cMyc expression. We further identified that cMyc stimulated SSP activation by transcriptionally upregulating expression of multiple SSP enzymes. Moreover, we demonstrated that SSP activation facilitated by cMyc led to elevated glutathione (GSH) production, cell cycle progression and nucleic acid synthesis, which are essential for cell survival and proliferation especially under nutrient-deprived conditions. We further uncovered that phosphoserine phosphatase (PSPH), the final rate-limiting enzyme of the SSP pathway, is critical for cMyc-driven cancer progression both in vitro and in vivo, and importantly, aberrant expression of PSPH is highly correlated with mortality in hepatocellular carcinoma (HCC) patients, suggesting a potential causal relation between this cMyc-regulated enzyme, or SSP activation in general, and cancer development. Taken together, our results reveal that aberrant expression of cMyc leads to the enhanced SSP activation, an essential part of metabolic switch, to facilitate cancer progressionunder nutrient-deprived conditions.