3-磷酸甘油酸脱氢酶促进丝氨酸合成在肿瘤进展中的机制

The mechanism of 3-phosphoglycerate dehydrogenase promoting serine synthesis in tumor progression

丝氨酸生物合成途径活性的上调是许多癌症明显的共同特征。该途径的第一种限速酶3-磷酸甘油酸脱氢酶(PHGDH)在黑色素瘤、乳腺癌和肾癌等癌组织中高表达,对肿瘤细胞增殖、转移、侵袭有着重要作用。糖酵解中间产物3-磷酸甘油酸在PHGDH作用下,氧化为磷酸羟基丙酮酸并最终合成丝氨酸。丝氨酸转化为甘氨酸,然后在核苷酸、s-腺苷甲硫氨酸(SAM)和还原型谷胱甘肽(GSH)的合成中起着重要的作用。PHGDH有望成为肿瘤治疗的新靶点。

Upregulation of serine biosynthetic pathway activity is a distinct common feature of many cancers.3-phosphoglycerate dehydrogenase(PHGDH),the first rate-limiting enzyme in this pathway,is highly expressed in melanoma,breast and kidney cancer.PHGDH plays an important role in tumor cell proliferation,metastasis and invasion.Glycolysis intermediate product 3-glyceric acid phosphate oxidized to hydroxypropionic acid phosphate under PHGDH action,and finally synthesized serine.Serine converted to glycine and then plays an important role in the synthesis of nucleotides,s-adenosylmethionine(SAM) and reduced glutathione(GSH).PHGDH is expected to be a new target for tumor therapy.