Targeting Stearoyl‐CoA Desaturase 1 Through PI3K‐AKT‐mTOR Signaling in Head and Neck Squamous Cell Carcinoma
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...
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| Format: | Article |
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Wiley
2025-04-01
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| Online Access: | https://doi.org/10.1002/oto2.70143 |
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| author | Cheng‐Ming Hsu Ming‐Yu Yang Shun‐Fu Chang Hui‐Chen Su |
| author_facet | Cheng‐Ming Hsu Ming‐Yu Yang Shun‐Fu Chang Hui‐Chen Su |
| author_sort | Cheng‐Ming Hsu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-eb0b84dcd16a49ab8fb85b2ec671b2e1 |
| institution | Matheson Library |
| issn | 2473-974X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | OTO Open |
| spelling | doaj-art-eb0b84dcd16a49ab8fb85b2ec671b2e12025-06-27T04:52:46ZengWileyOTO Open2473-974X2025-04-0192n/an/a10.1002/oto2.70143Targeting Stearoyl‐CoA Desaturase 1 Through PI3K‐AKT‐mTOR Signaling in Head and Neck Squamous Cell CarcinomaCheng‐Ming Hsu0Ming‐Yu Yang1Shun‐Fu Chang2Hui‐Chen Su3Department of Otolaryngology–Head and Neck Surgery Chiayi Chang Gung Memorial Hospital Chiayi TaiwanGraduate Institute of Clinical Medical Sciences, College of Medicine Chang Gung University Taoyuan TaiwanDepartment of Medical Research and Development Chiayi Chang Gung Memorial Hospital Chiayi TaiwanDepartment of Neurology, National Cheng‐Kung University Hospital, College of Medicine National Cheng Kung University Tainan TaiwanAbstract 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.https://doi.org/10.1002/oto2.70143head and neck squamous cell carcinoma (HNSCC)lipid metabolismPI3K‐AKT‐mTOR signalingstearoyl‐CoA desaturase 1 (SCD1)therapeutic target |
| spellingShingle | Cheng‐Ming Hsu Ming‐Yu Yang Shun‐Fu Chang Hui‐Chen Su Targeting Stearoyl‐CoA Desaturase 1 Through PI3K‐AKT‐mTOR Signaling in Head and Neck Squamous Cell Carcinoma OTO Open head and neck squamous cell carcinoma (HNSCC) lipid metabolism PI3K‐AKT‐mTOR signaling stearoyl‐CoA desaturase 1 (SCD1) therapeutic target |
| title | Targeting Stearoyl‐CoA Desaturase 1 Through PI3K‐AKT‐mTOR Signaling in Head and Neck Squamous Cell Carcinoma |
| title_full | Targeting Stearoyl‐CoA Desaturase 1 Through PI3K‐AKT‐mTOR Signaling in Head and Neck Squamous Cell Carcinoma |
| title_fullStr | Targeting Stearoyl‐CoA Desaturase 1 Through PI3K‐AKT‐mTOR Signaling in Head and Neck Squamous Cell Carcinoma |
| title_full_unstemmed | Targeting Stearoyl‐CoA Desaturase 1 Through PI3K‐AKT‐mTOR Signaling in Head and Neck Squamous Cell Carcinoma |
| title_short | Targeting Stearoyl‐CoA Desaturase 1 Through PI3K‐AKT‐mTOR Signaling in Head and Neck Squamous Cell Carcinoma |
| title_sort | targeting stearoyl coa desaturase 1 through pi3k akt mtor signaling in head and neck squamous cell carcinoma |
| topic | head and neck squamous cell carcinoma (HNSCC) lipid metabolism PI3K‐AKT‐mTOR signaling stearoyl‐CoA desaturase 1 (SCD1) therapeutic target |
| url | https://doi.org/10.1002/oto2.70143 |
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