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Gene & Protein in Disease GLUT5 in cancer development and therapy

suggested that dietary fructose promoted tumor immune by chemotherapy. All the above can be attributed to
evasion. In addition, the FBP1 level is directly associated the overexpression of GLUT5. Therefore, targeting
with cancer initiation and drug resistance in cervical GLUT5 represents a promising strategy to address
cancer, as demonstrated in a study analyzing 140 patients the multifaceted issues in cancer development and
with cervical cancer after radical surgery and subsequent progression, so as to improve cancer treatment and
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chemoradiation therapy. The results suggested that prevention. By far, the majority of evidence in this regard
FBP1 expression was not only associated with drug is derived from preclinical studies in mouse models or
resistance in cervical cancer but also the suppression of human patient tissue samples. Therefore, the GLUT5
the upregulated FBP1 in carcinogenesis and restoration expression may serve as a prognostic marker, particularly
of cancer cell chemosensitivity to cisplatin. In addition, in breast and colon cancer, with higher GLUT5 levels
an analysis of 222 colorectal cancer patient samples predicting poorer outcomes. To further explore the
showed that fructose-bisphosphate aldolase A played an potential of using GLUT5 as a therapeutic target, the
important role in the hypoxic adaptation in colorectal precise molecular mechanisms underlying GLUT5
cancer cells, serving as a potential target for treating overexpression-mediated cancer progression, metastasis,
drug resistance and improving poor prognosis. The and drug resistance need to be elucidated. Genomic
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study showed that ALDOA had negative impacts on drug and proteomic analyses can be conducted to identify
sensitivity and radiosensitivity and positive influence biomarkers related to fructose metabolism and GLUT5
on cell proliferation, colony formation, and migration. expression for the purposes of early cancer detection and
Similar effects were also observed in hepatocellular prognosis. Specific and potent GLUT5 inhibitors, for use
carcinoma under hypoxic conditions, which have impacts as an individual therapy or a combined treatment with
on tumor malignancy and renal cell carcinoma. Thus, existing chemotherapy and targeted therapies, should be
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targeting glucose metabolism in cancer cells offers a viable explored enhance therapeutic efficacy. Finally, dietary
approach to overcoming drug resistance. Besides, it has recommendations and public health policies may be
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been shown that inhibition of GLUT5 gene expression developed, such as dietary guidelines or regulatory
with trichostatin sensitized colon cancer cells to cisplatin policies to recommend lower consumption of fructose,
and oxaliplatin. Regardless of the impacts of GLUT5- particularly obtained from added sugars and processed
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mediated fructose mechanisms, dietary interventions foods.
could potentially contribute to cancer therapy. The
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relationships of key metabolic pathways, such as RAF- Acknowledgments
MEK-MAPK and PI3K-Akt-mTOR pathways, with None.
chemoresistance, as well as their potential as therapeutic
targets for lung cancers, have recently been reviewed. 80 Funding

5. Summary and future perspectives This work was supported in part by NSF-CBET 1915873.
Bao acknowledges Breast Cancer Research Foundation
GLUT5 represents an emerging and promising target of the University of Alabama Center for Convergent
in cancer therapy due to its role in fructose metabolism Bioscience and Medicine Pilot Innovation Fund.
and the fact that it is overexpressed in various cancers.
The upregulation of GLUT5 in various cancer cells Conflict of interest
enhanced fructose uptake and metabolism, which lead The authors declare no conflicts of interest.
to several cascade effects. First, the increased fructose
uptake promotes glycolysis, PPP activity, and lipogenesis, Author contributions
which collectively support tumor growth, survival, and
metastasis. Second, GLUT5 expression can influence the Conceptualization: Martin Guerrero, Gabrielle Kowkabany
Visualization: Martin Guerrero, Gabrielle Kowkabany
expression and activity of MMPs, facilitating cancer cell Writing – original draft: All authors
invasion and migration. In addition, fructose metabolism Writing – review & editing: Yuping Bao
enhances angiogenesis that provides pathways for cancer
cells to enter the bloodstream and metastasize. Finally, Ethics approval and consent to participate
the enhanced glycolysis leads to higher ATP production,
upregulating the expression of ABC transporters, such Not applicable.
as P-gp. Fructose metabolism increases NADPH levels, Consent for publication
resulting in higher glutathione levels for ROS reduction,
helping cancer cells to evade oxidative damage triggered Not applicable.

Volume 3 Issue 4 (2024) 9 doi: 10.36922/gpd.4171