Cell enlargement modulated by GATA4 and YAP instructs the senescence-associated secretory phenotype.

ABSTRACT: Dynamic changes in cell size are associated with development and pathological conditions, including aging. Although cell enlargement is a prominent morphological feature of cellular senescence, its functional implications are unknown; moreover, how senescent cells maintain their enlargement state is less understood. Here we show that an extensive remodeling of actin cytoskeleton is necessary for establishing senescence-associated cell enlargement and pro-inflammatory senescence-associated secretory phenotype (SASP). This remodeling is attributed to a balancing act between the SASP regulator GATA4 and the mechanosensor YAP on the expression of the Rho family of GTPase RHOU. Genetic or pharmacological interventions that reduce cell enlargement attenuate SASP with minimal effect on senescence

SUBMITTER: Joung J 

PROVIDER: S-EPMC11833096 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature