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The PHGDH enigma: Do cancer cells only need serine or also a redox modulator?

Abstract：

: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.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Li AM,Ye J

doi

10.1016/j.canlet.2020.01.036

subject

Has Abstract

pub_date

2020-04-28 00:00:00

pages

97-105

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(20)30050-1

journal_volume

476

pub_type

杂志文章

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