دورية أكاديمية
Co-Targeting FASN and mTOR Suppresses Uveal Melanoma Growth
| العنوان: | Co-Targeting FASN and mTOR Suppresses Uveal Melanoma Growth |
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| المؤلفون: | Anna Han, Dzmitry Mukha, Vivian Chua, Timothy J. Purwin, Manoela Tiago, Bhavik Modasia, Usman Baqai, Jenna L. Aumiller, Nelisa Bechtel, Emily Hunter, Meggie Danielson, Mizue Terai, Philip B. Wedegaertner, Takami Sato, Solange Landreville, Michael A. Davies, Stefan Kurtenbach, J. William Harbour, Zachary T. Schug, Andrew E. Aplin |
| المصدر: | Cancers, Vol 15, Iss 13, p 3451 (2023) |
| بيانات النشر: | MDPI AG, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | fatty acid synthase, mTOR pathway, metabolic inhibition, uveal melanoma, GNAQ, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Uveal melanoma (UM) displays a high frequency of metastasis; however, effective therapies for metastatic UM are limited. Identifying unique metabolic features of UM may provide a potential targeting strategy. A lipid metabolism protein expression signature was induced in a normal choroidal melanocyte (NCM) line transduced with GNAQ (Q209L), a driver in UM growth and development. Consistently, UM cells expressed elevated levels of fatty acid synthase (FASN) compared to NCMs. FASN upregulation was associated with increased mammalian target of rapamycin (mTOR) activation and sterol regulatory element-binding protein 1 (SREBP1) levels. FASN and mTOR inhibitors alone significantly reduced UM cell growth. Concurrent inhibition of FASN and mTOR further reduced UM cell growth by promoting cell cycle arrest and inhibiting glucose utilization, TCA cycle metabolism, and de novo fatty acid biosynthesis. Our findings indicate that FASN is important for UM cell growth and co-inhibition of FASN and mTOR signaling may be considered for treatment of UM. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 15133451 2072-6694 |
| Relation: | https://www.mdpi.com/2072-6694/15/13/3451; https://doaj.org/toc/2072-6694 |
| DOI: | 10.3390/cancers15133451 |
| URL الوصول: | https://doaj.org/article/bd1520908be04ad1b023ec228e9a8999 |
| رقم الأكسشن: | edsdoj.bd1520908be04ad1b023ec228e9a8999 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15133451 20726694 |
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| DOI: | 10.3390/cancers15133451 |