Page 22 - GPD-3-4

Gene & Protein in Disease

REVIEW ARTICLE
The roles of GLUT5 in cancer progression,

metastasis, and drug resistance

Martin Guerrero, Gabrielle Kowkabany, and Yuping Bao*
Department of Chemical and Biological Engineering, College of Engineering, The University of
Alabama, Tuscaloosa, Alabama, United States of America

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
*Corresponding author:
Yuping Bao therapeutic potential of GLUT 5-mediated fructose metabolism in cancer therapy. In
(ybao@eng.ua.edu) particular, targeting GLUT 5 and its-associated processes in fructose metabolism may
Citation: Guerrero M, offer promising strategies for improving cancer treatment outcomes through dietary
Kowkabany G, Bao Y. The roles interventions, specific GLUT5 inhibitors, or in combination.
of GLUT5 in cancer progression,
metastasis, and drug resistance.
Gene Protein Dis. 2024;3(4):4171. Keywords: Fructose metabolism; GLUT5 expression; Cancer progression; Cancer metastasis;
doi: 10.36922/gpd.4171
Drug resistance; Epithelial-mesenchymal transition; Matrix metalloproteinases;
Received: July 8, 2024 Pentose phosphate pathway
Accepted: September 18, 2024
Published Online: October 15, 2024
Copyright: © 2024 Author(s).
This is an Open-Access article 1. Introduction
distributed under the terms of the
Creative Commons Attribution Common in human diet, fructose is a natural nutrient that can be obtained from fruits,
License, permitting distribution,
and reproduction in any medium, honey, and vegetables; however, the increased intake of fructose from processed foods
1
provided the original work is and drinks becomes an increasing concern. The increased fructose intake directly results
properly cited. in abnormal expression of glucose transporter 5 (GLUT5), encoded by the solute carrier
Publisher’s Note: AccScience family 2 member 5 (SLC2A5) gene for specific fructose transport, in tissues that typically
Publishing remains neutral with do not express GLUT5. On the other hand, the upregulation of GLUT5 leads to further
2
regard to jurisdictional claims in 3
published maps and institutional fructose utilization. Compared to glucose that can be metabolized throughout the body,
affiliations. only certain tissues express GLUT5 and are able to metabolize fructose, such as small

Volume 3 Issue 4 (2024) 1 doi: 10.36922/gpd.4171