Journal
CANCER LETTERS
Volume 476, Issue -, Pages 97-105Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.01.036
Keywords
PHGDH; Serine; Cancer metabolism; PSAT1; PSPH; One carbon unit
Categories
Funding
- NIH T32 Training Grant [CA009302-40]
- NIH R00 Grant [CA184239]
- Mary Kay Foundation Innovative Cancer Research Award [017-37]
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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 (alpha KG) 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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