Paracrine roles of cellular senescence in promoting tumourigenesis

Abstract

Senescent cells activate genetic programmes that irreversibly inhibit cellular proliferation, but also endow these cells with distinctive metabolic and signalling phenotypes. Although senescence has historically been considered a protective mechanism against tumourigenesis, the activities of senescent cells are increasingly being associated with age-related diseases, including cancer. An important feature of senescent cells is the secretion of a vast array of pro-inflammatory cytokines, chemokines, and growth factors collectively known as the senescence-associated secretory phenotype (SASP). Recent research has shown that SASP paracrine signalling can mediate several pro-tumourigenic effects, such as enhancing malignant phenotypes and promoting tumour initiation. In this review, we summarise the paracrine activities of senescent cells and their role in tumourigenesis through direct effects on growth and proliferation of tumour cells, tumour angiogenesis, invasion and metastasis, cellular reprogramming and emergence of tumour-initiating cells, and tumour interactions with the local immune environment. The evidence described here suggests cellular senescence acts as a double-edged sword in cancer pathogenesis, which demands further attention in order to support the use of senolytic or SASP-modulating compounds for cancer treatment.