Fatty Acid Metabolism Provides an Essential Survival Signal in OxPhos and BCR DLBCL Cells
Year: 2025
Type: article
Abstract: Diffuse large B-cell lymphoma (DLBCL) is the most frequent subtype of malignant lymphoma and is a heterogeneous disease with various gene and chromosomal abnormalities. The development of novel therapeutic treatments has improved DLBCL prognosis, but patients with early relapse or refractory disease have a poor outcome (with a mortality of ~ 40%). Metabolic reprogramming is a hallmark of cancer cells. Fatty acid (FA) metabolism is frequently altered in cancer cells and recently emerged as a critical survival path for cancer cell survival. Here, we reveal using a large panel of DLBCL cell lines characterized for their metabolic status that targeting of FA metabolism induces massive DLBCL cell death, regardless of their OxPhos or BCR/glycolytic subtype. Further, FA drives resistance of DLBCL cell death induced by mitochondrial stress upon treatment with either metformin or L-asparaginase, two FDA-approved antimetabolic drugs. Interestingly, combining inhibition of FA metabolism with that of the mTOR oncogenic pathway strongly potentiates DLBCL cell death. Altogether our data highlight the central role played by FA metabolism in DLBCL cell survival, independently of their metabolic subtype, and provide the framework for the use of drugs targeting this metabolic vulnerability to overcome resistance in DLBCL patients.
Source: Biomedicines
Institutions: Université Paris Cité, NF-kappaB, Différenciation et Cancer, Inserm, Institut Gustave Roussy, Sorbonne Université, Centre de Recherche des Cordeliers, Centro de Investigación Biomédica en Red de Cáncer, Centro de Investigación Médica Aplicada, Universidad de Navarra, Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges-Pompidou, Hôpital Saint-Louis
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,137
Funders: Association pour la Recherche sur le Cancer, Seerave Foundation, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Fondation ARC pour la Recherche sur le Cancer, Ligue Contre le Cancer, Institut Universitaire de France, Institut National Du Cancer, Cancéropôle Ile de France, Direction Générale de l’offre de Soins, Centro de Investigación Biomédica en Red de Cáncer, Instituto de Salud Carlos III, Labex Immuno-Oncology
Awards: G1056382719, G1152389130, G1168482666, G1366152532, G1397743473, Next-generation phenotypic screening for oncological applications, G1647832332, G1716190585, G1738818464, G1846858737, G1984256294, G2109069054, G2161503289, G2179318311, G2203660494, G2203820474, Lung cancer prevention and interception, G2335174368, G2351262490, G2370373925, G2575938703, G2669570515, G2699422577, G2707798878, G2714391379, G2776565293, G2777467966, G282393413, G2992841218, G3231222199, G323126134, Mitochondrial copper targeting to modulate inflammatory macrophages, G3281827434, G330243840, G3499571000, G3536394303, G3599999703, G3615399218, G36935394, G3772543176, G3920652601, G4007257112, G4039294350, G4054977659, G4202018978, G4205215534, G420978141, G4280170732, G4284054818, G4364925233, G4394515762, G461710914, G4744413284, G4746608011, G4752693786, G4753522887, G4900465205, G4990482369, G5121171980, G5265134632, G540687550, Microbiota-centered interventions to solve antibiotics-induced primary resistance to immune checkpoint inhibitors, G5468290041, G5474765000, G5566697476, Energizing the failing heart, G5767140378, G5770080219, G5790172013, G5855436522, G5868083567, G5868422650, G5953624409, G5990937808, G6072338176, G6081517606, G609205739, G6148319146, G6279142687, G6292965458, G6300110603, G6318539078, G6467557300, G6558284573, G668953012, G6718544961, G6850463825, G69196502, G7017386022, G7041469554, G7075379671, G7101784390, G7309355080, G7319818416, G7339467324, G7371525705, G7568831491, G7662726268, G7839273552, G816800923, G8447641012, Université de Paris, G8560148563, G8633455951, G8809306651, The RUSH (retention using selective hooks) system: a chemical-genetic system for the in vivo manipulation of intercellular communication, G8829892426, G8855315112, G8900920507, G8991455713, G915670629, G945336879, G968191185
OpenAlex ID: W4408409898