In summary, our results unveiled a previously unappreciated interplay between lipid metabolic and metastatic program, as well as the existence of a pivotal C/EBPδ-Slug-Lox1 transcription axis to promote oxLDL levels and cancer metastasis.
For the first time, we have observed that LOX-1 inhibition significantly prevents metastasis formation in injected mice and, at the same time, induces a downregulation of VEGF-A165, HIF-1α, and β-catenin whose expression is involved in cell migration and metastasis, and a variation of histone H4 acetylation pattern suggesting also a role of LOX-1 in regulating gene transcription.
In conclusion, our results suggest that oxLDL/LOX-1 could be ones of mechanisms that explain why obese patients with prostate cancer have an accelerated tumor progression and a greater probability of developing metastasis.
Lectin-like oxidized low-density lipoprotein receptor-1 facilitates metastasis of gastric cancer through driving epithelial-mesenchymal transition and PI3K/Akt/GSK3β activation.