PDGFRβ modulates aerobic glycolysis in osteosarcoma HOS cells via the PI3K/AKT/mTOR/c-Myc pathway

Abstract

Osteosarcoma is a malignant tumor abundant in vascular tissue, and its rich blood supply may have a significant impact on its metabolic characteristics. PDGFRβ is a membrane receptor highly expressed in osteosarcoma cells and vascular wall cells, and its effect on osteosarcoma metabolism needs to be further studied. In this study, we discussed the effect and mechanism of action of PDGFRβ on glucose metabolism in human osteosarcoma (HOS) cells. GSEA, Pearson’s correlation test, and PPI correlation analysis indicated positive regulation of PDGFRβ on aerobic glycolysis in osteosarcoma. The results of qPCR and western blot further confirmed the prediction of bioinformatics. Glucose metabolism experiments proved that PDGF/PDGFRβ could effectively promote aerobic glycolysis in osteosarcoma cells. In addition, the mitochondrial membrane potential (ΔΨm) experiment proved that the metabolic change triggered by PDGFRβ was not caused by mitochondrial damage. The PI3K pathway inhibitor LY294002, MEK pathway inhibitor U0126, or Warburg effect inhibitor DCA was used to perform western blot and glucose metabolism experiments, and the results showed that PDGFBB/PDGFRβ mainly activated the PI3K/AKT/mTOR/c-Myc pathway to promote aerobic glycolysis in osteosarcoma HOS cells. The newly elucidated role of PDGFRβ provides a novel metabolic therapeutic target for osteosarcoma.

S100 calcium-binding protein A10 contributes to malignant traits in osteosarcoma cells by regulating glycolytic metabolism via the AKT/mTOR pathway

“…The AKT/mTOR pathway is deeply involved in the regulation of proliferation, migration, invasion, and apoptosis in tumor cells [ 44 ]. Besides, the AKT/mTOR pathway also participates in glycolytic regulation in OSa [ 45 ]. For example, Wang et al revealed that Arbutin treatment inhibited OSa cell proliferation and metastasis by downregulating MTHFD1L via miR-338-3p and inactivating the AKT/mTOR signaling [ 46 ].…”

Metabolic reprogramming in osteosarcoma

“…GLUT1 can be activated by oncogenes cMyc and HIF‐1ɑ 23 . Circ‐ECE1, Her4, and PDGFRβ increase glucose uptake and promote metabolic reprogramming in OS through cMyc 24–26 . MiR‐186, KRT17 and TGF‐β promote glucose uptake and glycolysis in OS cells via HIF‐1ɑ 27–29 .…”

“…23 Circ-ECE1, Her4, and PDGFRβ increase glucose uptake and promote metabolic reprogramming in OS through cMyc. [24][25][26] MiR-186, KRT17 and TGF-β promote glucose uptake and glycolysis in OS cells via HIF-1ɑ. [27][28][29] The miR-200c plays a central role in glucose metabolism in cancer cells, and CircCSPP1 may influence miR-200c maturation to regulate glucose uptake and cell proliferation to promote OS.…”

The roles of glycolysis in osteosarcoma

“…As an important intracellular transcription factor, c-myc promotes glycolysis by transactivating and promoting the expression of genes related to glycolysis ( Gruning et al, 2010 ; Han et al, 2012 ). Furthermore, as the target of several oncogenes or tumor suppressor genes, c-myc participates in regulating many signal pathways, such as MEK-ERK, Wnt/β-catenin, PI3K/AKT/mTOR, and STAT3/c-myc ( Han et al, 2012 ; Li K. et al, 2021 ; Tang et al, 2022 ). In 2012, Han et al (2012) found that c-myc overexpression in OS significantly enhanced the invasive ability of OS cells by promoting the MEK-ERK pathway.…”