Relationship between Fructose Metabolism Pathway and Hepatocellular Carcinoma and Colorectal Cancer

Jinhan Jiang; Zihao Qu; Ziyang Xie

doi:10.54097/0t4acb48

Authors

Jinhan Jiang
Zihao Qu
Ziyang Xie

DOI:

https://doi.org/10.54097/0t4acb48

Keywords:

Tumor Microenvironment; Fructose metabolism; Hepatocellular carcinoma; Colorectal cancer; Metabolic reprogramming.

Abstract

Colorectal cancer and liver cancer have become the second and the third primary causes of cancer death around the world. In recent years, the important role and mechanism of fructose in cancer and other diseases have also attracted widespread interests, but the interaction between fructose metabolism and the development of colorectal cancer and liver cancer remains unclear. This review discusses the research progress in recent years on the mechanism of fructose metabolism in promoting hepatocellular carcinoma and colorectal cancer, including i) Promoting cancer cell growth through indirect effects such as promoting O-GlcNAcylation via microbial-derived acetate and inhibiting M1-like tumor-associated macrophage polarization. ii) Directly affecting cancer cell metabolic reprogramming by regulating metabolic-related enzymes (aldolase B, KHK-A) and upregulating reactive oxygen species (ROS). This review summarizes the different promotion of fructose metabolism in the Growth-Colorectal cancer liver metastasis-Colonization process of colorectal cancer.The future research directions and priorities around fructose metabolism are discussed and proposed at the end of this review, indicating the importance and potential value of fructose metabolism in cancer development research.

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References

[1] Baharuddin, B., The Impact of Fructose Consumption on Human Health: Effects on Obesity, Hyperglycemia, Diabetes, Uric Acid, and Oxidative Stress With a Focus on the Liver. Cureus, 2024. 16(9): p. e70095.

[2] Fowle-Grider, R., et al., Dietary fructose enhances tumour growth indirectly via interorgan lipid transfer. Nature, 2024. 636(8043): p. 737-744.

[3] Yan, H., et al., Hexokinase 2 senses fructose in tumor-associated macrophages to promote colorectal cancer growth. Cell Metab, 2024. 36(11): p. 2449-2467 e6.

[4] Socha-Banasiak, A., et al., Intestinal fructose transporters GLUT5 and GLUT2 in children and adolescents with obesity and metabolic disorders. Adv Med Sci, 2024. 69(2): p. 349-355.

[5] Federico, A., et al., The Role of Fructose in Non-Alcoholic Steatohepatitis: Old Relationship and New Insights. Nutrients, 2021. 13(4).

[6] Nomura, K. and T. Yamanouchi, The role of fructose-enriched diets in mechanisms of nonalcoholic fatty liver disease. J Nutr Biochem, 2012. 23(3): p. 203-8.

[7] Nomura, N., et al., Structure and mechanism of the mammalian fructose transporter GLUT5. Nature, 2015. 526(7573): p. 397-401.

[8] Wang, N., et al., AMPK-a key factor in crosstalk between tumor cell energy metabolism and immune microenvironment? Cell Death Discov, 2024. 10(1): p. 237.

[9] Zhao, Q., et al., AKR1B1-dependent fructose metabolism enhances malignancy of cancer cells. Cell Death Differ, 2024. 31(12): p. 1611-1624.

[10] Kang, Y.L., et al., The polyol pathway and nuclear ketohexokinase A signaling drive hyperglycemia-induced metastasis of gastric cancer. Exp Mol Med, 2024. 56(1): p. 220-234.

[11] Frezza, C., Fructose: the sweet(er) side of the Warburg effect. Cell Death Differ, 2024. 31(11): p. 1395-1397.

[12] Charrez, B., L. Qiao, and L. Hebbard, The role of fructose in metabolism and cancer. Horm Mol Biol Clin Investig, 2015. 22(2): p. 79-89.

[13] Zhou, P., et al., High dietary fructose promotes hepatocellular carcinoma progression by enhancing O-GlcNAcylation via microbiota-derived acetate. Cell Metab, 2023. 35(11): p. 1961-1975 e6.

[14] Kim, J., et al., Ketohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer. Nat Commun, 2020. 11(1): p. 5436.

[15] Muriel, P., P. Lopez-Sanchez, and E. Ramos-Tovar, Fructose and the Liver. Int J Mol Sci, 2021. 22(13).

[16] Tao, Q.F., et al., Aldolase B inhibits metastasis through Ten-Eleven Translocation 1 and serves as a prognostic biomarker in hepatocellular carcinoma. Mol Cancer, 2015. 14: p. 170.

[17] Huang, X.H. and C.Y. Huang, Fructose shields human colorectal cancer cells from hypoxia-induced necroptosis. NPJ Sci Food, 2024. 8(1): p. 71.

[18] Peng, C., et al., KHK-A promotes fructose-dependent colorectal cancer liver metastasis by facilitating the phosphorylation and translocation of PKM2. Acta Pharm Sin B, 2024. 14(7): p. 2959-2976.

[19] He, R., et al., Glycolysis reprogramming in CAFs promotes oxaliplatin resistance in pancreatic cancer through circABCC4 mediated PKM2 nuclear translocation. Cell Death Dis, 2025. 16(1): p. 126.