Károlyi, Dorottya and Bótor, Sólyom Bálint and Neuhauser, Natali and Rubics, András and Szinyákovics, Janka and Kovács, Tibor and Péter, Mária and Balogh, Gábor and O’Farrell, Fergal and Takáts, Szabolcs (2026) Fatty acid synthesis supports tumor progression through facilitating the activity of TORC1 signaling. CELL DEATH AND DISEASE, 17 (1). ISSN 2041-4889
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Abstract
Biosynthesis of lipids and fatty acids (FAs) is essential for the normal functioning of cellular processes, and lipid availability determines the progression of multiple malignant tumor types. To date, the roles of individual steps in lipid biosynthesis during tumor growth and their interaction with intracellular signaling pathways are not well understood. Our study demonstrates that upregulation of de novo FA and lipid synthesis is a conserved characteristic of malignant tumors. In vivo tumor cell-specific silencing of components of the neutral lipid biosynthetic apparatus revealed that loss of several enzymes involved in FA and diacylglycerol synthesis inhibited tumor growth. Specifically, acetyl-CoA carboxylase (ACC), which catalyzes the first step of FA synthesis, drives late-stage tumor growth. FA synthesis perturbation led to inactivation of TORC1 (mechanistic Target of Rapamycin Complex 1)—accompanied by activation of the catabolic process autophagy. Moreover, TORC1 activity cannot be fully restored by hyperactivation of upstream Insulin/PI3K signaling or inhibition of AMP-activated kinase (AMPK) in ACC-deficient tumor cells, but supplementation with ectopic oleic acid can partially increase TORC1 activity and tumor progression. In addition to their metabolic value, the role of FAs in promoting TORC1 gives us new insight into cancer cell dependence on de novo FA synthesis.
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| Additional Information: | Funding Agency and Grant Number: This author used the device of Single Cell Omics Advanced Core Facility of the Hungarian Centre of Excellence for Molecular Medicine (HCEMM) that has received funding from the EU's Horizon 2020 research and innovation program (Grant Reference Number: 73959; Norges Forskningsrd (Research Council of Norway) [324447]; Excellence Fund of Etvs Lornd University (Grant Reference Number: EKA_2023/071-P025-1); Nemzeti Kutatsi, Fejlesztsi s Innovcis Hivatal (NKFI Office) [ANN_139553, TKP2021-EGA-09, STARTING 150612]; Academy of Finland (AKA) [324447] Funding Source: Academy of Finland (AKA) Funding text: This research was funded by the National Research, Development and Innovation Office of Hungary (OTKA FK_142508 to ST, OTKA ANN 139553 and TKP2021-EGA-09 to GB, STARTING 150612 to TK and EKOP-25-2-I-ELTE-80 to NN), the Hungarian Academy of Sciences (BO/00400/23 to ST), and the Excellence Fund of Eotvos Lorand University (EKA_2022/045-P302-1 to ST and EKA_2023/071-P025-1 for TK). FOF was supported by a Norwegian Research Council Grant "Decoding tumor cell invasive switching" Project No.: 324447. We thank the Single Cell Omics Advanced Core Facility staff of the HCEMM for help with their resources and their support. HCEMM has received funding from the EU's Horizon 2020 research and innovation program under grant agreement No. 739593 and the Ministry of Culture and Innovation of Hungary (Grant reference number: KIM NKFIA 2022-2.1.1-NL-2022-00005). Open access funding provided by Eotvos Lorand University. |
| Subjects: | Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0254 Neoplasms. Tumors. Oncology (including Cancer) / daganatok, tumorok, onkológia |
| SWORD Depositor: | MTMT SWORD |
| Depositing User: | MTMT SWORD |
| Date Deposited: | 07 Sep 2026 07:48 |
| Last Modified: | 07 Sep 2026 07:48 |
| URI: | https://real.mtak.hu/id/eprint/245564 |
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