The tumor microenvironment and cancer-associated fibroblasts (CAFs) play crucial roles in tumor development, and their metabolic coupling remains unclear. Clinical data showed a positive correlation between PDGF-BB, CAFs, and glycolysis in the tumor microenvironment of oral tongue squamous cell carcinoma patients. In vitro, CAFs are derived from hOMF cells treated with PDGF-BB, which induces their formation and promotes aerobic glycolysis. Mitophagy increased the PDGF-BB-induced formation of CAF phenotypes and aerobic glycolysis, while autophagy inhibition blocked PDGF-BB-induced effects. Downregulation of miR-26a-5p was observed in CAFs; upregulation of miR-26a-5p inhibited the expression of mitophagy-related proteins ULKI, Parkin, PINK1, and LC3 and aerobic glycolysis in PDGF-BB-induced CAFs. PDGF-BB-induced CAFs promoted tumor cell proliferation, invasion, metastasis, NF-κB signaling pathway activation, and PDGF-BB secretion. Thus, PDGF-BB is associated with lactate-induced CAF formation and glucose metabolism reprogramming. These findings indicate potential therapeutic targets in oral tongue squamous cell carcinoma.
Keyphrases
- growth factor
- signaling pathway
- smooth muscle
- squamous cell carcinoma
- vascular smooth muscle cells
- cell proliferation
- high glucose
- diabetic rats
- recombinant human
- drug induced
- induced apoptosis
- oxidative stress
- poor prognosis
- pi k akt
- high intensity
- newly diagnosed
- epithelial mesenchymal transition
- mass spectrometry
- cell death
- radiation therapy
- immune response
- locally advanced
- ejection fraction
- toll like receptor
- big data
- long non coding rna
- risk assessment
- high resolution mass spectrometry