Cited by 271Cancer, Hypoxia, and MetabolismMetabolism, Diabetes, and CancerBiochemical and Molecular Research

Balancing glycolytic flux: the role of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatases in cancer metabolism

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Ros, Susana, Schulze, Almut·2013·Cancer & Metabolism

Abstract

The increased glucose metabolism in cancer cells is required to fulfill their high energetic and biosynthetic demands. Changes in the metabolic activity of cancer cells are caused by the activation of oncogenes or loss of tumor suppressors. They can also be part of the metabolic adaptations to the conditions imposed by the tumor microenvironment, such as the hypoxia response. Among the metabolic enzymes that are modulated by these factors are the 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatases (PFKFBs), a family of bifunctional enzymes that control the levels of fructose 2,6-bisphosphate (Fru-2,6-P2). This metabolite is important for the dynamic regulation of glycolytic flux by allosterically activating the rate-limiting enzyme of glycolysis phosphofructokinase-1 (PFK-1). Therapeutic strategies designed to alter the levels of this metabolite are likely to interfere with the metabolic balance of cancer cells, and could lead to a reduction in cancer cell proliferation, invasiveness and survival. This article will review our current understanding of the role of PFKFB proteins in the control of cancer metabolism and discuss the emerging interest in these enzymes as potential targets for the development of antineoplastic agents.

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Crossref · 10.1186/2049-3002-1-8

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  • The PFK-2/FBPase-2 family comprises PFKFB1, PFKFB2, PFKFB3 and PFKFB4, all of which are induced by HIF-1 under hypoxic conditions.

    “The PFK-2/FBPase-2 family comprises several enzyme isoforms, PFKFB1, PFKFB2, PFKFB3 and PFKFB4, all of which are induced by HIF-1 under hypoxic conditions [101].”

    From HIF-1-Independent Mechanisms Regulating Metabolic Adaptation in Hypoxic Cancer Cells (2021) · cites this paper as [101]

    The PFKFB genes section identifies PFKFB1–PFKFB4 as the four genes encoding this enzyme family. The PFK-2/FBPase-2 enzymes in hypoxia section reports hypoxic induction of mRNAs from all four genes, but identifies only PFKFB3 and PFKFB4 as components of the HIF-mediated response. It does not establish that HIF-1 induces PFKFB1 or PFKFB2. (LLM, conf=0.90)

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Authors
Ros, S., & Schulze, A.
Affiliations
Cancer Research UK (GB)
Corresponding author
Schulze, Almut
Venue
Cancer & Metabolism
Published
2013-02-04
Volume
1
Issue
1
Pages
8-8
ISSN
2049-3002 (ISSN-L)
OpenAlex
W2106223802
Cited by
269
References
69
Citations by year
2026: 9 · 2025: 21 · 2024: 29 · 2023: 32 · 2022: 31 · 2021: 26 · 2020: 15 · 2019: 20 · 2018: 17 · 2017: 17 · 2016: 19 · 2015: 20 · 2014: 11 · 2013: 2
FWCI
6.22
Type
journal article
Language
en
Open access
Locations
  • Cancer & Metabolism (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo (cc-by)
Funders
Cancer Research UK
Topics
  • 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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Keywords
6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, fructose-2,6-bisphosphate, glycolytic flux, tumor microenvironment, hypoxia response, oncogene activation, tumor suppressor loss

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