Document Type

Article

Publication Date

6-30-2023

Comments

This article is the author's final published version in Cancers, Volume 15, Issue 13, 2023, Article number 3451.

The published version is available at https://doi.org/10.3390/cancers15133451. Copyright © 2023 by the authors. Licensee MDPI, Basel, Switzerland.

Abstract

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.

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Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

Additional Files
cancers-2466949-supplementary.pdf (2803 kB)
Supplementary Materials

Language

English

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