Title :

The transcription factor ChREBP Orchestrates liver carcinogenesis by coordinating the PI3K/AKT signaling and cancer metabolism

Author(s) :

Benichou, Emmanuel [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Seffou, Bolaji [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Topçu, Selin [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Renoult, Ophélie [Auteur]
Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers [CRCI2NA]
Lenoir, Véronique [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Planchais, Julien [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Bonner, Caroline [Auteur]
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]
Institut Pasteur de Lille
Université de Lille
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Postic, Catherine [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Prip-Buus, Carina [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Pecqueur, Claire [Auteur]
Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers [CRCI2NA]
Guilmeau, Sandra [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Alves-Guerra, Marie-Clotilde [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Dentin, Renaud [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]

Journal title :

Nature Communications

Pages :

1879

Publisher :

Nature Publishing Group

Publication date :

2024-02-29

ISSN :

2041-1723

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Cancer cells integrate multiple biosynthetic demands to drive unrestricted proliferation. How these cellular processes crosstalk to fuel cancer cell growth is still not fully understood. Here, we uncover the mechanisms by ...
Show more >Cancer cells integrate multiple biosynthetic demands to drive unrestricted proliferation. How these cellular processes crosstalk to fuel cancer cell growth is still not fully understood. Here, we uncover the mechanisms by which the transcription factor Carbohydrate responsive element binding protein (ChREBP) functions as an oncogene during hepatocellular carcinoma (HCC) development. Mechanistically, ChREBP triggers the expression of the PI3K regulatory subunit p85α, to sustain the activity of the pro-oncogenic PI3K/AKT signaling pathway in HCC. In parallel, increased ChREBP activity reroutes glucose and glutamine metabolic fluxes into fatty acid and nucleic acid synthesis to support PI3K/AKT-mediated HCC growth. Thus, HCC cells have a ChREBP-driven circuitry that ensures balanced coordination between PI3K/AKT signaling and appropriate cell anabolism to support HCC development. Finally, pharmacological inhibition of ChREBP by SBI-993 significantly suppresses in vivo HCC tumor growth. Overall, we show that targeting ChREBP with specific inhibitors provides an attractive therapeutic window for HCC treatment.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (RNMCD) - U1011

Source :

Harvested from HAL