Work

NFIC activates DEPTOR and blocks mTOR signaling to inhibit glycolysis and immune escape in oral squamous cell carcinoma

Year: 2025

Type: article

Abstract: Objective Oral squamous cell carcinoma (OSCC) has a poor prognosis and high mortality. This study aims to investigate the potential molecular mechanisms of NFIC/DEPTOR/mTOR signaling in glycolysis and tumor immune escape in OSCC. Design In vitro , the effects of the NFIC/DEPTOR/mTOR axis on the proliferative capacity and apoptosis of HN30 and SCC-25 cells were investigated using colony formation assays, EdU staining, and TUNEL after lentiviral gene interference. The glycolytic activity of OSCC cells was analyzed through glucose uptake, ECAR, and lactate production. CD8 + T cells were co-cultured with OSCC cells to analyze the cytotoxic activity of CD8 + T cells. SCC-25 cells with different genetic interventions were injected subcutaneously into NOG mice to investigate the effects of NFIC/DEPTOR/mTOR on subcutaneous tumor growth, tumor microenvironment (TME) acidity, and CD8 + T cell infiltration and activity. ChIP-qPCR and dual-luciferase assays were used to investigate the regulatory relationship between NFIC and the DEPTOR promoter in OSCC cells. Results NFIC and DEPTOR were significantly downregulated in OSCC cells and tissues, accompanied by enhanced mTOR signaling. NFIC activated DEPTOR by binding to its promoter. Overexpression of either NFIC or DEPTOR significantly inhibited OSCC cell proliferation, glycolytic activity, and enhanced CD8 + T cell killing capacity. Similarly, they inhibited tumor growth in vivo , blocked TME acidification, and weakened tumor immune escape. Combined DEPTOR knockdown rescued the malignant progression of OSCC inhibited by NFIC overexpression. Conclusion NFIC mediates DEPTOR transcription to repress mTOR signaling, thereby hindering OSCC progression by suppressing cell proliferation, glycolytic activity, and CD8 + T cell-related immune escape.

Source: Archives of Oral Biology

DOI: 10.1016/j.archoralbio.2025.106442

Authors: Jian Xu, Mohang Sun, Xin Wang, Yuxin Zou, Lina Wang

Institutions: Harbin Medical University, Second Affiliated Hospital of Harbin Medical University, Heilongjiang Provincial Hospital

Language: English

Topic: PI3K/AKT/mTOR signaling in cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,760