Cited by 351Biochemical and Molecular ResearchCancer, Hypoxia, and MetabolismMetabolism, Diabetes, and Cancer

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The molecular determinants of de novo nucleotide biosynthesis in cancer cells

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Tong, Xuemei, Zhao, Fangping, Thompson, Craig B·2009·Current Opinion in Genetics & Development

DOI 10.1016/j.gde.2009.01.002PMC PMC2707261

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Abstract

Tumor cells increase the use of anabolic pathways to satisfy the metabolic requirements associated with a high growth rate. Transformed cells take up and metabolize nutrients such as glucose and glutamine at high levels that support anabolic growth. Oncogenic signaling through the PI3K/Akt and Myc pathways directly control glucose and glutamine uptake, respectively. In order to achieve elevated rates of nucleotide biosynthesis, neoplastic cells must divert carbon from PI3K/Akt-induced glycolytic flux into the nonoxidative branch of the pentose phosphate pathway to generate ribose-5-phosphate. This redirection of glucose catabolism appears to be regulated by cytoplasmic tyrosine kinases. Myc-induced glutamine metabolism also increases the abundance and activity of different rate-limiting enzymes that produce the molecular precursors required for de novo nucleotide synthesis. In this review, we will focus on recent progress in understanding how glucose and glutamine metabolism is redirected by oncogenes in order to support de novo nucleotide biosynthesis during proliferation and how metabolic reprogramming can be potentially exploited in the development of new cancer therapies.

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Authors: Tong, X., Zhao, F., & Thompson, C. B.
Affiliations: Abramson Cancer Center (US)
Corresponding author: Tong, Xuemei
Zhao, Fangping
Thompson, Craig B
ORCID: Tong, Xuemei
Thompson, Craig B
Venue: Current Opinion in Genetics & Development
Publisher: Elsevier BV
Published: 2009-02
Volume: 19
Issue: 1
Pages: 32-37
ISSN: 0959-437X (ISSN-L)
DOI: 10.1016/j.gde.2009.01.002
PMC: PMC2707261
OpenAlex: W2002869675
Cited by: 351
References: 56
Citations by year: 2026: 13 · 2025: 14 · 2024: 22 · 2023: 20 · 2022: 22 · 2021: 24 · 2020: 32 · 2019: 20 · 2018: 18 · 2017: 15 · 2016: 17 · 2015: 26 · 2014: 17 · 2013: 15 · 2012: 33
FWCI: 1.91
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Current Opinion in Genetics & Development (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (R01CA092660)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: cancer metabolism, metabolic reprogramming, PI3K/Akt signaling, c-Myc, glucose metabolism, glutamine metabolism, pentose phosphate pathway, ribose-5-phosphate, glycolysis, oncogenic signaling, cancer therapy
MeSH terms: Animals, Cell Transformation, Neoplastic, Glucose, Glutamine, Glycolysis, Humans, Models, Biological, Neoplasms, Pentose Phosphate Pathway, Ribosemonophosphates, Proto-Oncogene Proteins c-myc, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Proto-Oncogene Proteins c-akt

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The molecular determinants of de novo nucleotide biosynthesis in cancer cells

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