Fructose Metabolism in Cancer

Krause, Nils; Wegner, André

doi:10.3390/cells9122635

Cited by 53 publications

(38 citation statements)

References 100 publications

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“…We previously reported that cancer cells such as acute myeloid leukemia cells exhibited enhanced fructose utilization under low glucose conditions and that pharmacologic blockade of fructose utilization suppressed AML cell proliferation and enhanced the therapeutic efficacy of Ara-C 2 . Our recent findings, along with reports from other groups 1–4 , suggest that fructose is a preferred carbon source for many cancer cells. High expression of the fructose transporter SLC2A5/GLUT5 was found in multiple types of cancers, enabling increased uptake of fructose from the microenvironment and enhanced cancer growth and development.…”

supporting

confidence: 79%

Fructose Metabolism Contributes to the Warburg effect

Han

Wang

Zhang

et al. 2020

Preprint

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SUMMARYFructose metabolism is increasingly recognized as a preferred energy source for cancer cell proliferation. However, dietary fructose rarely enters the bloodstream, and its fasting blood levels are much lower (~0.005 mM) than glucose (~5.5 mM) under normal physiological conditions. Therefore, it remains unclear where fructose is derived from and how cancer cells acquire a sufficient amount of fructose to supplement their energy needs. Here we report that the polyol pathway is active in cancer cells and is capable of converting up to 50% of glucose into fructose, resulting in enhanced glycolysis and ATP production. Inhibition of the polyol pathway severely decreased fructose production in cancer cells and suppressed their glycolysis, ATP production, and growth rate. Furthermore, we determined that the glucose transporter, SLC2A8/GLUT8, was a crucial transporter to export intracellular fructose outside cells. Taken together, our study identified an overlooked but critically essential fructose-producing pathway in cancer cells as an integral part of their metabolic reprogramming leading to enhanced glycolysis, cell proliferation, and malignancy.

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supporting

confidence: 79%

Fructose Metabolism Contributes to the Warburg effect

Han

Wang

Zhang

et al. 2020

Preprint

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“…This enzyme hydrogenates Fructose to Sorbitol in Fructose catabolism pathway. Subsequently, sorbitol is dehydrogenated to glucose via AKR1B1 enzyme providing fuel for cells ( 132 ). In addition, excess glucose promotes EMT through autocrine TGFβ stimulation ( 133 ).…”

Section: Discussionmentioning

confidence: 99%

Systems Biomedicine of Primary and Metastatic Colorectal Cancer Reveals Potential Therapeutic Targets

et al. 2021

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Colorectal cancer (CRC) is one of the major causes of cancer deaths across the world. Patients’ survival at time of diagnosis depends mainly on stage of the tumor. Therefore, understanding the molecular mechanisms from low-grade to high-grade stages of cancer that lead to cellular migration from one tissue/organ to another tissue/organ is essential for implementing therapeutic approaches. To this end, we performed a unique meta-analysis flowchart by identifying differentially expressed genes (DEGs) between normal, primary (primary sites), and metastatic samples (Colorectal metastatic lesions in liver and lung) in some Test datasets. DEGs were employed to construct a protein-protein interaction (PPI) network. A smaller network containing 39 DEGs was then extracted from the PPI network whose nodes expression induction or suppression alone or in combination with each other would inhibit tumor progression or metastasis. These DEGs were then verified by gene expression profiling, survival analysis, and multiple Validation datasets. We suggested for the first time that downregulation of mitochondrial genes, including ETHE1, SQOR, TST, and GPX3, would help colorectal cancer cells to produce more energy under hypoxic conditions through mechanisms that are different from “Warburg Effect”. Augmentation of given antioxidants and repression of P4HA1 and COL1A2 genes could be a choice of CRC treatment. Moreover, promoting active GSK-3β together with expression control of EIF2B would prevent EMT. We also proposed that OAS1 expression enhancement can induce the anti-cancer effects of interferon-gamma, while suppression of CTSH hinders formation of focal adhesions. ATF5 expression suppression sensitizes cancer cells to anchorage-dependent death signals, while LGALS4 induction recovers cell-cell junctions. These inhibitions and inductions would be another combinatory mechanism that inhibits EMT and cell migration. Furthermore, expression inhibition of TMPO, TOP2A, RFC3, GINS1, and CKS2 genes could prevent tumor growth. Besides, TRIB3 suppression would be a promising target for anti−angiogenic therapy. SORD is a poorly studied enzyme in cancer, found to be upregulated in CRC. Finally, TMEM131 and DARS genes were identified in this study whose roles have never been interrogated in any kind of cancer, neither as a biomarker nor curative target. All the mentioned mechanisms must be further validated by experimental wet-lab techniques.

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“…Some of these metabolic changes involve the increased consumption of fructose in low glucose conditions or the regulation of enzymes to support alternative metabolic pathways. There have been comprehensive studies and reviews documenting the role of fructose in cancer metabolism [ 59 , 60 , 61 , 62 ]; therefore, we will briefly focus on some recent findings related to fructose metabolism through central carbon pathways. Since the consumption of fructose has increased over the past decades, understanding how cancers metabolize fructose has become more critical and encourages a consideration of dietary changes or alternative therapeutic strategies that might target fructose-related pathways to mitigate cancer progression.…”

Section: Fructose Metabolism Disordersmentioning

confidence: 99%

Fructose and Mannose in Inborn Errors of Metabolism and Cancer

et al. 2021

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History suggests that tasteful properties of sugar have been domesticated as far back as 8000 BCE. With origins in New Guinea, the cultivation of sugar quickly spread over centuries of conquest and trade. The product, which quickly integrated into common foods and onto kitchen tables, is sucrose, which is made up of glucose and fructose dimers. While sugar is commonly associated with flavor, there is a myriad of biochemical properties that explain how sugars as biological molecules function in physiological contexts. Substantial research and reviews have been done on the role of glucose in disease. This review aims to describe the role of its isomers, fructose and mannose, in the context of inborn errors of metabolism and other metabolic diseases, such as cancer. While structurally similar, fructose and mannose give rise to very differing biochemical properties and understanding these differences will guide the development of more effective therapies for metabolic disease. We will discuss pathophysiology linked to perturbations in fructose and mannose metabolism, diagnostic tools, and treatment options of the diseases.

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Fructose Metabolism in Cancer

Cited by 53 publications

References 100 publications

Fructose Metabolism Contributes to the Warburg effect

Fructose Metabolism Contributes to the Warburg effect

Systems Biomedicine of Primary and Metastatic Colorectal Cancer Reveals Potential Therapeutic Targets

Fructose and Mannose in Inborn Errors of Metabolism and Cancer

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