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

First Author  Li AM Year  2020
Journal  Cancer Lett Volume  476
Pages  97-105 PubMed ID  32032680
Mgi Jnum  J:285840 Mgi Id  MGI:6400396
Doi  10.1016/j.canlet.2020.01.036 Citation  Li AM, et al. (2020) The PHGDH enigma: Do cancer cells only need serine or also a redox modulator?. Cancer Lett 476:97-105
abstractText  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 (alphaKG) 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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