PFKFB4 promotes endometrial cancer by regulating glycolysis through SRC‑3 phosphorylation.

Abstract

The present study aimed to investigate the role of 6‑phosphofructo‑2‑kinase/fructose‑2,6‑biphosphatase 4 (PFKFB4) in endometrial cancer cells and to explore its potential molecular mechanisms. PFKFB4 expression in endometrial cancer tissues was detected by immunohistochemistry. Cell Counting Kit‑8, Transwell assays and flow cytometry were used to detect cell proliferation, invasion and apoptosis in endometrial cancer cells after PFKFB4 knockdown. An enzyme‑linked immunosorbent assay was used to detect the glucose and lactic acid contents. Western blotting was performed to detect the levels of glycolysis‑related enzymes, steroid receptor coactivator‑3 (SRC‑3), and phosphorylated SRC‑3. In vivo experiments were performed to investigate the tumorigenic potential of PFKFB4. PFKFB4 expression was upregulated in endometrial cancer tissues compared with that in normal controls, and its upregulation was positively correlated with the depth of myometrial invasion, lymph node metastasis, surgical pathological stage and vascular invasion. PFKFB4 knockdown significantly inhibited proliferation and invasion, increased apoptosis, and decreased oxygen consumption and lactic acid production in endometrial cancer cells. PFKFB4 knockdown decreased SRC‑3 phosphorylation. After simultaneous PFKFB4 knockdown and SRC‑3 overexpression in cancer cells, oxygen consumption, lactic acid production, and glycolysis‑related protein expression were increased compared with those in control cells. PFKFB4 knockdown inhibited tumor proliferation, apoptosis and the expression of Ki‑67. PFKFB4 may regulate glycolysis in endometrial cancer cells by targeting SRC‑3, thus promoting endometrial cancer progression.