Stearoyl‐CoA Desaturase‐1 Drives Tumor Growth by Interacting With Histone Deacetylase‐2 and Deacetylating Nucleophosmin‐1

Wery, Coline; Montero-Ruiz, Laetitia; Bonneil, Eric; Farran, Mohammad; Jehay, Robin; Garfia, Quentin Herrara; Fettweis, Grégory; Blacher, Silvia; Pottier, Charles; Cobraiville, Gaël; Boumahd, Yasmine; Peulen, Olivier; Noël, Agnès; Dequiedt, Franck; Fillet, Marianne; Sounni, Nor Eddine

doi:10.1002/mco2.70809

Article (Scientific journals)

Stearoyl‐CoA Desaturase‐1 Drives Tumor Growth by Interacting With Histone Deacetylase‐2 and Deacetylating Nucleophosmin‐1

Wery, Coline; Montero-Ruiz, Laetitia; Bonneil, Eric et al.

2026 • In MedComm, 7 (6)

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/346704

DOI
10.1002/mco2.70809

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Keywords :

Lipid metabolism; Hypoxia; stearoyl‐CoA desaturase‐1 (SCD1); Lipid droplet; NPM1; HDAC2; Vorinostat; PLIN2; non-histone protein deacetylation/acetylation

Abstract :

[en] ABSTRACT The adaptation of lipid metabolism in cancer cells, driven by changes in the tumor microenvironment, presents major challenges for cancer therapy. Here, we addressed the problem of altered lipid metabolism and its role in cancer progression and therapeutic resistance. We demonstrate that hypoxia upregulates the key desaturase, stearoyl‐CoA desaturase‐1 (SCD1), and the lipid droplet (LD) protein PLIN2, thus promoting lipid metabolic adaptation, cell proliferation, migration, and tumor growth. We found that SCD1 and PLIN2 are essential and interdependent for LD formation. PLIN2 supports cell survival under hypoxic and metabolic stress, whereas SCD1 sustains cancer cell proliferation upon reoxygenation. In addition, we found that SCD1 expression in cancer cells affects nonhistone protein deacetylation, whereas PLIN2 expression enhances protein acetylation. Among these proteins, nucleophosmin(NPM1), a tumor suppressor and regulator of p53, was destabilized through SCD1‐dependent deacetylation. In addition, SCD1 interacts with NPM1, influences its cellular localization, and recruits histone deacetylase‐2 (HDAC2) to the complex. Notably, we observed that knockdown of SCD1 in vitro or its pharmacological inhibition in vivo enhances cancer cell sensitivity to HDAC inhibitors. Our findings underscore the role of SCD1 in reshaping the cellular acetylome and suggest that targeting SCD1 could sensitize cancer cells to HDAC inhibitors, highlighting a promising therapeutic strategy.

Research Center/Unit :

GIGA-Cancer Metabolism and Tumor Microenvironment

Disciplines :

Oncology

Author, co-author :

Wery, Coline ; Université de Liège - ULiège > GIGA

Montero-Ruiz, Laetitia ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire

Bonneil, Eric; Institute for Research in Immunology and Cancer (IRIC) University of Montréal Montréal Canada

Farran, Mohammad ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire

Jehay, Robin ; Université de Liège - ULiège > GIGA > GIGA Cancer - Tumors Biology and Development

Garfia, Quentin Herrara; Cancer Metabolism and Tumor Microenvironment Lab GIGA‐Cancer GIGA Institute University of Liège Liège Belgium

Fettweis, Grégory ; Université de Liège - ULiège > Département des sciences de la vie

Blacher, Silvia ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire

Pottier, Charles ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire

Cobraiville, Gaël ; Université de Liège - ULiège > GIGA > GIGA Immunobiology - Rheumatology

More authors (6 more)

Language :

English

Title :

Stearoyl‐CoA Desaturase‐1 Drives Tumor Growth by Interacting With Histone Deacetylase‐2 and Deacetylating Nucleophosmin‐1

Publication date :

June 2026

Journal title :

MedComm

eISSN :

2688-2663

Publisher :

Wiley

Volume :

Issue :

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://onlinelibrary.wiley.com/doi/pdf/10.1002/mco2.70809

Funders :

FWB - Fédération Wallonie-Bruxelles
F.R.S.-FNRS - Fonds de la Recherche Scientifique

Available on ORBi :

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