The alternative NF-κB RelB subunit is a novel critical sensor of lipid metabolism to promote tumor development
Abstract
Cancer cells reprogram their metabolism to fulfill their high energetic demand. Lipid metabolism is most often reprogrammed for cancer cell survival and tumor development. The role of alternative oncogenic NF-κB/RelB subunit in the reprogramming of lipid metabolism in cancer is unknown. Here we report that RelB plays a central role at the crossroads of lipid storage and liberation of fatty acids from the lipid droplets to feed the fatty acid oxidation (FAO) and mitochondrial energetic metabolism. High RelB expression defines a subset of hepatocellular carcinoma (HCC) patients and cell lines with a peculiar gene expression profile enriched in lipid catabolic-related genes, including lipases. Functional studies revealed that high RelB activation controls the expression of major lipolytic lipases, including adipose triglyceride lipase (ATGL) and monoglyceride lipase (MAGL), and impacts on HCC cell survival, migration, and tumor development in vivo. Altogether, we uncovered that RelB is a central regulator of the lipid metabolism plasticity and an energy homeostasis sensor in cancer cells.
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BibTeX
@article{becquard2026alternative,
title = {{The alternative NF-κB RelB subunit is a novel critical sensor of lipid metabolism to promote tumor development}},
author = {T. Becquard and C. Benatar and C. Bretot and B. Eluard and D. Bordereaux and L. Thirouard and A. Hammoutene and A. Montagne and F. Dingli and D. Loew and C. Ransy and M.-C Alves-Guerra and C. Caradeuc and N. Cagnard and M. Boissan and N. Giraud and F. Bouillaud and G. Bertho and V. Paradis and D. Chiron and R. Dentin and C. Prip-Buus and V. Baud},
journal = {Cell Death and Disease},
year = {2026},
month = jul,
doi = {10.1038/s41419-026-09064-7},
url = {https://hal.science/hal-05759902v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The alternative NF-κB RelB subunit is a novel critical sensor of lipid metabolism to promote tumor development
AU - T. Becquard
AU - C. Benatar
AU - C. Bretot
AU - B. Eluard
AU - D. Bordereaux
AU - L. Thirouard
AU - A. Hammoutene
AU - A. Montagne
AU - F. Dingli
AU - D. Loew
AU - C. Ransy
AU - M.-C Alves-Guerra
AU - C. Caradeuc
AU - N. Cagnard
AU - M. Boissan
AU - N. Giraud
AU - F. Bouillaud
AU - G. Bertho
AU - V. Paradis
AU - D. Chiron
AU - R. Dentin
AU - C. Prip-Buus
AU - V. Baud
PY - 2026
DA - 2026/07/04
JO - Cell Death and Disease
DO - 10.1038/s41419-026-09064-7
UR - https://hal.science/hal-05759902v1
AB - Cancer cells reprogram their metabolism to fulfill their high energetic demand. Lipid metabolism is most often reprogrammed for cancer cell survival and tumor development. The role of alternative oncogenic NF-κB/RelB subunit in the reprogramming of lipid metabolism in cancer is unknown. Here we report that RelB plays a central role at the crossroads of lipid storage and liberation of fatty acids from the lipid droplets to feed the fatty acid oxidation (FAO) and mitochondrial energetic metabolism. High RelB expression defines a subset of hepatocellular carcinoma (HCC) patients and cell lines with a peculiar gene expression profile enriched in lipid catabolic-related genes, including lipases. Functional studies revealed that high RelB activation controls the expression of major lipolytic lipases, including adipose triglyceride lipase (ATGL) and monoglyceride lipase (MAGL), and impacts on HCC cell survival, migration, and tumor development in vivo. Altogether, we uncovered that RelB is a central regulator of the lipid metabolism plasticity and an energy homeostasis sensor in cancer cells.
SN - 2041-4889
ER -