Paradoxical activation of AMPK by glucose drives selective EP300 activity in colorectal cancer - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles PLoS Biology Year : 2020

Paradoxical activation of AMPK by glucose drives selective EP300 activity in colorectal cancer

Abstract

Coordination of gene expression with nutrient availability supports proliferation and homeostasis and is shaped by protein acetylation. Yet how physiological/pathological signals link acetylation to specific gene expression programs and whether such responses are cell-type-specific is unclear. AMP-activated protein kinase (AMPK) is a key energy sensor, activated by glucose limitation to resolve nutrient supply-demand imbalances, critical for diabetes and cancer. Unexpectedly, we show here that, in gastrointestinal cancer cells, glucose activates AMPK to selectively induce EP300, but not CREB-binding protein (CBP). Consequently, EP300 is redirected away from nuclear receptors that promote differentiation towards β-catenin, a driver of proliferation and colorectal tumorigenesis. Importantly, blocking glycogen synthesis permits reactive oxygen species (ROS) accumulation and AMPK activation in response to glucose in previously nonresponsive cells. Notably, glycogen content and activity of the ROS/AMPK/EP300/β-catenin axis are opposite in healthy versus tumor sections. Glycogen content reduction from healthy to tumor tissue may explain AMPK switching from tumor suppressor to activator during tumor evolution.
Fichier principal
Vignette du fichier
journal.pbio.3000732 (2).pdf (5.46 Mo) Télécharger le fichier
Origin : Publication funded by an institution
Loading...

Dates and versions

inserm-02908725 , version 1 (29-07-2020)

Identifiers

Cite

María Gutiérrez-Salmerón, José Manuel García-Martínez, Javier Martínez-Useros, María Jesús Fernández-Aceñero, Benoit Viollet, et al.. Paradoxical activation of AMPK by glucose drives selective EP300 activity in colorectal cancer. PLoS Biology, 2020, 18 (6), pp.e3000732. ⟨10.1371/journal.pbio.3000732⟩. ⟨inserm-02908725⟩
27 View
55 Download

Altmetric

Share

Gmail Facebook X LinkedIn More