The Proinflammatory Secretome of Senescent Cells Can Be Controlled by a HIF2A-Dependent Upregulation and a FURIN-Dependent Cleavage of the ANGPTL4 Secreted Factor.

ABSTRACT: Senescent cells are characterized by a stable proliferation arrest and a senescence-associated secretory phenotype or SASP. Although these cells can have some beneficial effects, including protecting from tumor formation, their accumulation is deleterious during aging as it promotes age-related diseases, including cancer initiation and progression. Although the SASP has a critical role, its composition, regulation and dual role in cancer remain largely misunderstood. Here, we show that ANGPTL4 is one of the rare secreted factors induced in many different types of senescent cells. Importantly, ANGPTL4 knockdown during senescence or its constitutive expression, respectively inhibits or induces classical proinflammatory SASP factors, such as IL1A, IL6 and IL8. The latter effect is mediated up

SUBMITTER: Makulyte G 

PROVIDER: S-EPMC12741039 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature