Surfeit 4 regulates aerobic glycolysis to enhanced proliferation, tumor stemness, invasion, and metastasis in oral squamous cell carcinoma

Abstract

Objective: Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide. Surfeit 4 (SURF4) is a member of the surfeit gene family and plays a regulatory role in various cellular processes, such as protein transport and lipid metabolism. Therefore, this study aims to investigate the regulatory role and mechanisms of SURF4 in OSCC. Material and Methods: Serum samples were collected from the normal control and OSCC groups. The function of OSCCs was analyzed through Transwell, 5-ethynyl-2’-deoxyuridine incorporation, and Cell Counting Kit-8 assays. Selected proteins were measured by Western blot analysis. Additional vectors for the overexpression (OE) and knockdown of SURF4 were established. Aerobic glycolysis (AG) was detected through cellular glucose consumption and lactate production assays. Results: A significant increase was observed in protein and messenger RNA (mRNA) levels of serum SURF4 in OSCC patients compared with the control group (P < 0.001). The knockdown of SURF4 alleviated proliferation, invasion, and metastasis in OSCC (P < 0.001). Overexpressing SURF4 aggravated proliferation and invasion in OSCC and increased the levels of stem cell genes Octamer-binding Transcription Factor 4 and Sex-determining Region Y-box 2 (P < 0.001). Furthermore, adenosine triphosphate levels, lactate levels, and extracellular acidification rate were found to be elevated in the OE SURF4 group, along with higher levels of AG-related regulatory proteins (P < 0.001). Inhibiting AG with glycolysis inhibitor 2-deoxyglucose effectively impeded proliferation and invasion in OSCC. Conclusion: SURF4 plays a role in OSCC by regulating AG to enhance proliferation, tumor stemness, invasion, and metastasis.