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
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
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,对于维持营养匮乏肿瘤转移相关基因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(生物谷bioon.com)
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
linchong sun1,*, libing song2,*, qianfen wan3, gongwei wu1, xinghua li2, yinghui wang1, jin wang3, zhaoji liu1, xiuying zhong1, xiaoping he1, shengqi shen1, 肿瘤医院xin pan4, ailing li4, yulan wang3,5, ping gao1, huiru tang3,6 and huafeng zhang1
doi: 10.1038/cr.2015.33
2015年3月27日讯 /生物谷bioon/ --近日,中国科学技术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
cancer cells are known to undergo metabolic reprogramming to sustain survival an膀胱肿瘤术后护理d 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 p膀胱肿瘤电切术athway (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, c外阴肿瘤的危害ell 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 pro复大肿瘤医院gression 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 togeth肿瘤相关抗原199er, our results reveal that aberrant expression of cmyc leads to the enhanced ssp activation, an essential part of metabolic switch, to facilitate cancer progression under nutrient-deprived conditions.
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cmyc-mediated activation of serine biosynthesis pathway肿瘤相关抗原125 is critical for cancer progression under nutrient deprivation conditions
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