Analysis of malignant melanoma cell lines exposed to hypoxia reveals the importance of PFKFB4 overexpression for disease progression

Abstract

Background/Aim: Most melanomas develop in hypoxic conditions. Since hypoxia via HIF-1 induces glycolysis, a process essential for malignant melanoma growth/survival, the goal of this study was to analyze the influence of hypoxia on the expression of HIF-1 target genes involved in glucose metabolism. Materials and Methods: The response of melanoma cell lines to hypoxic conditions was analyzed by RT-PCR and western blotting. A Kaplan–Meier survival analysis for patients with high and low expression level of PFKFB4 was performed. Further analysis of patients’ data was performed using the R/Bioconductor environment. Results: Induction of PFKFB4 gene expression can be considered a crucial mechanism behind glycolysis enhancement in hypoxic melanoma cells. Analysis of a publicly available database revealed that high PFKFB4 expression contributes to poor prognosis of melanoma patients. Conclusion: Currently available anti-melanoma therapeutic strategies may significantly benefit from agents targeting PFKFB4 activity.