Biological and clinical significance of the AGE-RAGE axis in the aggressiveness and prognosis of prostate cancer

Shih Hong Khoo, Pei Ru Wu, Kun Tu Yeh, Shih Lan Hsu, Chi Hao Wu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Dietary factors and chronic hyperglycemia are linked to the formation of advanced glycation end products (AGEs) and prostate cancer (PCa) risk. The activation of the receptor for AGEs (RAGE) acts as a bridge between various RAGE ligands and certain malignancies. This study showed that the interaction of AGEs and RAGE promoted PCa cell proliferation, invasion, and autophagy-mediated survival in response to chemotherapeutic agents. RAGE-overexpressed PCa cells underwent epithelialemesenchymal transition and showed increased cancer stem cell-like properties. In mouse xenograft models, RAGE-overexpressed cells showed more substantial tumorigenic capacity than parental cells, whereas RAGE knockdown decreased tumorigenicity. The clinical data validated a positive correlation between high AGE and RAGE expressions with poor clinical outcomes. Our findings suggest that the AGE-RAGE axis facilitates PCa progression and aggressiveness. Prostatic AGEs and RAGE expression levels are associated with PCa prognosis. Adherence to a reduced-AGE diet and targeting RAGE are potential approaches to complement and synergize with the current PCa therapies.

Original languageEnglish
Pages (from-to)664-682
Number of pages19
JournalJournal of Food and Drug Analysis
Volume31
Issue number4
DOIs
Publication statusPublished - 2023

Keywords

  • Advanced glycation end products
  • Aggressiveness
  • Glycative stress
  • Prostate cancer
  • RAGE

ASJC Scopus subject areas

  • Food Science
  • Pharmacology

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