丝氨酸
下调和上调
限制
焊剂(冶金)
癌细胞
生物
癌症
生物合成
癌症研究
酶
细胞生物学
生物化学
化学
基因
遗传学
有机化学
工程类
机械工程
作者
Albert M. Li,Jiangbin Ye
标识
DOI:10.1016/j.canlet.2020.01.036
摘要
Upregulation of serine biosynthesis pathway activity is an increasingly apparent feature of many cancers. Most notably, the first rate-limiting enzyme of the pathway, phosphoglycerate dehydrogenase (PHGDH), is genomically amplified in some melanomas and breast cancers and can be transcriptionally regulated by various tumor suppressors and oncogenes. Yet emerging evidence suggests that serine—in particular, serine biosynthetic pathway activity—may promote cancer in ways beyond providing the building blocks to support cell proliferation. Here, we summarize how mammalian cells tightly control serine synthesis before discussing alternate ways in which increased serine synthetic flux through PHGDH may benefit cancer cells, such as maintenance of TCA cycle flux through alpha-ketoglutarate (αKG) and modulation of cellular redox balance. We will also provide an overview of the current landscape of therapeutics targeting serine synthesis and offer a perspective on future strategies.
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