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Targeting Stearoyl‐CoA Desaturase 1 Through PI3K‐AKT‐mTOR Signaling in Head and Neck Squamous Cell Carcinoma

Year: 2025

Type: article

Abstract: Objective: Stearoyl-coenzyme A desaturase 1 (SCD1) is a key enzyme in fatty acid metabolism and has been implicated in cancer progression, including head and neck squamous cell carcinoma (HNSCC). The phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) signaling pathway is a critical regulator of cellular metabolism and survival in cancer. This study investigates the crosstalk between SCD1 inhibition and the PI3K-AKT-mTOR pathway, highlighting the therapeutic potential of targeting SCD1 in HNSCC. Study Design: Basic science. Setting: Laboratory. Methods: Four HNSCC cell lines were utilized to evaluate the relationship between SCD1 and the mTOR signaling pathway. Cell viability was assessed following treatment with various mTOR inhibitors. The effect of AKT-mTOR signaling on SCD1 expression was examined through pharmacological inhibition and gene silencing approaches. Additionally, the impact of SCD1 knockdown on cell proliferation and survival was analyzed. Results: mTOR inhibitors significantly reduced HNSCC cell viability and downregulated SCD1 expression in a dose-dependent manner. Inhibition of AKT, a key upstream effector of mTOR, also suppressed SCD1 expression, suggesting that SCD1 is regulated through the PI3K-AKT-mTOR axis. Silencing SCD1 independently impaired cancer cell growth and enhanced the cytotoxic effects of mTOR inhibitors, indicating a synergistic anticancer effect. Conclusion: SCD1 is a downstream target of the PI3K-AKT-mTOR pathway and contributes to HNSCC cell survival. Dual targeting of SCD1 and the mTOR signaling pathway represents a promising therapeutic strategy for HNSCC treatment. Further investigation is warranted to explore the clinical potential of SCD1 inhibitors in combination with mTOR-targeted therapies.

Source: OTO Open

DOI: 10.1002/oto2.70143

Authors: Cheng‐Ming Hsu, Ming‐Yu Yang, Shun‐Fu Chang, Hui‐Chen Su