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Comment
. 2011 Sep 7;14(3):285-6.
doi: 10.1016/j.cmet.2011.08.004.

Serine metabolism: some tumors take the road less traveled

Ralph J DeBerardinis  1
Affiliations
Comment

Serine metabolism: some tumors take the road less traveled

Ralph J DeBerardinis. Cell Metab. .

Abstract

Cancer cells display a reprogramming of metabolism that facilitates growth but addicts them to key enzyme activities. Two studies in Nature and Nature Genetics find that the gene encoding the serine biosynthetic enzyme phosphoglycerate dehydrogenase (PHGDH) is amplified in a subset of cancers and contributes to tumor cell growth.

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Figures

Figure 1
Figure 1. Role of PHGDH in tumor cell metabolism
Many tumors have enhanced expression of the metabolic enzyme phosphoglycerate (PHGDH), in some cases because the gene encoding this enzyme is amplified on chromosome 1p12. PHGDH diverts flux away from glycolysis by oxidizing 3-phosphoglycerate (3-PG) to 3-phospho-hydroxypyruvate (3-POHPyr). Subsequent metabolism of this 3-carbon intermediate feeds into the serine and glycine pools, providing numerous precursor molecules and other substrates required for cell growth and proliferation. Abbreviations: Ac-CoA, acetyl-CoA; αKG, α-ketoglutarate; DHAP, dihydroxyacetone phosphate; GA3P, glyceraldehyde-3-phosphate; NH4+, ammonium ion; N5N10-MTHF, N5,N10-methylene tetrahydrofolate; OAA, oxaloacetate; PEP, phosphoenolpyruvate; PSAT1, phosphoserine aminotransferase-1; SAM, S-adenosylmethionine; SHMT, serine hydroxymethyltransferase; THF, tetrahydrofolate.
See this image and copyright information in PMC

Comment on

  • Functional genomics reveal that the serine synthesis pathway is essential in breast cancer.
    Possemato R, Marks KM, Shaul YD, Pacold ME, Kim D, Birsoy K, Sethumadhavan S, Woo HK, Jang HG, Jha AK, Chen WW, Barrett FG, Stransky N, Tsun ZY, Cowley GS, Barretina J, Kalaany NY, Hsu PP, Ottina K, Chan AM, Yuan B, Garraway LA, Root DE, Mino-Kenudson M, Brachtel EF, Driggers EM, Sabatini DM. Possemato R, et al. Nature. 2011 Aug 18;476(7360):346-50. doi: 10.1038/nature10350. Nature. 2011. PMID: 21760589 Free PMC article.
  • Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis.
    Locasale JW, Grassian AR, Melman T, Lyssiotis CA, Mattaini KR, Bass AJ, Heffron G, Metallo CM, Muranen T, Sharfi H, Sasaki AT, Anastasiou D, Mullarky E, Vokes NI, Sasaki M, Beroukhim R, Stephanopoulos G, Ligon AH, Meyerson M, Richardson AL, Chin L, Wagner G, Asara JM, Brugge JS, Cantley LC, Vander Heiden MG. Locasale JW, et al. Nat Genet. 2011 Jul 31;43(9):869-74. doi: 10.1038/ng.890. Nat Genet. 2011. PMID: 21804546 Free PMC article.

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