Science and Technology Production
Congress
Authorship
Date
2025
Publishing House and Editing Place
Fundación Revista Medicina
ISSN
1669-9106
Summary
Information provided by the agent in
SIGEVA
AKR1B1 catalyzes the reduction of aldehydes to alcohols and has been implicated in tumor progression, although its precise role in cancer remains insufficiently explored. Our group has shown that AKR1B1promotes tumor growth and metastasis in vivo. While it catalyzes the rate-limiting step of the polyol pathway, reducing glucose to sorbitol, AKR1B1 also reduces diverse substrates such as glyceraldehyde, methylglyoxal, prostaglandin H, and lipid peroxides. This broad substrate specificity complic...
AKR1B1 catalyzes the reduction of aldehydes to alcohols and has been implicated in tumor progression, although its precise role in cancer remains insufficiently explored. Our group has shown that AKR1B1promotes tumor growth and metastasis in vivo. While it catalyzes the rate-limiting step of the polyol pathway, reducing glucose to sorbitol, AKR1B1 also reduces diverse substrates such as glyceraldehyde, methylglyoxal, prostaglandin H, and lipid peroxides. This broad substrate specificity complicates the understanding of its pathological contribution. To dissect the molecular mechanisms underlying the pro-oncogenic activity of AKR1B1, we performed a proteomic analysis. Using liquid chromatography?mass spectrometry, we examined the effects of AKR1B1 overexpression in murine triple-negative breast cancer 4T1 cells. We found a strong impact on the proteomic landscape, with several differentially expressed proteins detected. Functional enrichment analysis identified ?metabolic pathways? asthe most significantly enriched category, highlighting alterations inthe mitochondrial electron transport chain and lipid metabolism. To assess the clinical significance of AKR1B1, we analyzed breast cancer patient datasets. Elevated AKR1B1 mRNA expression was significantly associated with reduced survival, especially in patients with lymph node invasion (p = 7.7× 10⁻⁶, log-rank test). We also investigated factors affectingAKR1B1 expression. In cell lines, glucose restriction decreased AKR1B1 expression, as shown by qPCR and luciferase assays. In summary, our study indicates that AKR1B1 overexpression has a profound impact on the expression of proteins associated with mitochondrial function and lipid metabolism. Moreover, it provides evidence suggesting a significant effect of AKR1B1 overexpression on breast cancer patient survival.
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Key Words
PROTEOMICSBREAST CANCERAKR1B1METASTASIS