AccScience Publishing / GPD / Online First / DOI: 10.36922/gpd.4171
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REVIEW

The roles of GLUT5 in cancer progression, metastasis, and drug resistance

Martin Guerrero1 ,  Gabrielle Kowkabany1 ,  Yuping Bao1*
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1 Department of Chemical and Biological Engineering, College of Engineering, The University of Alabama, Tuscaloosa, Alabama, United States of America
GPD, 4171 https://doi.org/10.36922/gpd.4171
Submitted: 8 July 2024 | Accepted: 18 September 2024 | Published: 15 October 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Emerging evidence has suggested that high fructose intake, particularly from added sugars and processed foods, is associated with increased cancer risk and progression. The fructose intake is believed to be mediated by the abnormal expression of glucose transporter 5 (GLUT5), the specific fructose transporter in cancer cells. The GLUT5-regulated fructose metabolism has shown to greatly affect cancer progression, metastasis, and drug resistance. This review aims to synchronize the current knowledge to highlight the underlying mechanisms of those impacts and understand the therapeutic potential of GULT5. First, we review the fructose metabolism and its alteration in cancer cells by comparing with glucose metabolism. Subsequently, the key contributors or biological pathways involved in GLUT5-asosociated tumor growth, cancer metastasis, and drug resistance are discussed. The contributions of specific pathways, metabolites, and key enzymes from the fructose metabolism process are also covered, such as enhanced glycolysis for tumor growth, epithelial-mesenchymal transition and angiogenesis for cancer metastasis, and efflux pump expression and activation of survival pathways for cancer drug resistance. The detailed analysis of these mechanisms will allow further understanding of the therapeutic potential of GLUT 5-mediated fructose metabolism in cancer therapy. In particular, targeting GLUT 5 and its-associated processes in fructose metabolism may offer promising strategies for improving cancer treatment outcomes through dietary interventions, specific GLUT5 inhibitors, or in combination.

Keywords
Fructose metabolism
GLUT5 expression
Cancer progression
Cancer metastasis
Drug resistance
Epithelial-mesenchymal transition
Matrix metalloproteinases
Pentose phosphate pathway
Funding
This work was supported in part by NSF-CBET 1915873. Bao acknowledges Breast Cancer Research Foundation of the University of Alabama Center for Convergent Bioscience and Medicine Pilot Innovation Fund.
Conflict of interest
The authors declare no conflicts of interest.
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