Senescence and cancer: An evolving inflammatory paradox

Abstract

The senescent phenotype was first describe in 1961 as a phenomenon characterized by the cessation of cellular division. After years of debate as to whether it represented a tissue culture artifact or an important biological process, it is now appreciated that senescence plays an important role in tumorigenesis. Further, senescence is integral to normal biological processes such as embryogenesis and the maintenance of tissue homeostasis. Now with defined roles in development, wound healing, tumor promotion and tumor suppression, it is not surprising that attention has turned to refining our understanding of the mechanisms behind, and consequences of, the induction of senescence. One emerging role for senescence lies in the ability of senescence to orchestrate an inflammatory responses: factors secreted by senescent cells have been identifed in multiple contexts to modulate various aspects of immune response. As with many of the previously described roles for senescence, the type of inflammation established by the senescence phenotype is varied and dependent on context. In this review, we discuss the current state of the field with a focus on the paradoxical outcomes of the senescence-induced inflammatory responses in the context of cancer. A more complete understanding of senescence and an appreciation for its complexities will be important for eventual development of senescence-targeted therapies.

Stromal-Initiated Changes in the Bone Promote Metastatic Niche Development

“…SASP is characterized by expression of a wide variety of inflammatory cytokines, growth factors, and extracellular matrix remodeling enzymes. While each of these categories is expressed in cells undergoing senescence, the exact factors vary depending on the cell of origin and the tissue under scrutiny (Coppe et al, 2008; Kuilman et al, 2008; Rodier and Campisi, 2011; Ruhland et al, 2015). Because cell cycle inhibitors including p16IN4a and p21 do not induce SASP (Coppe et al, 2011), we wanted to ensure that p27 Kip1 induced SASP.…”

Role of p53 in the Regulation of Cellular Senescence

“…It is responsible for many chronic diseases, including cardiovascular and bowel diseases, diabetes, arthritis, and cancer [114,115]. The connection between inflammation and cellular senescence was initially suggested by studies on the gene expression profiles of senescent cells, where inflammatory responses were associated with wound healing processes [116]. In inflammatory conditions, the senescence mechanism can be activated by either oncogene or inflammatory mediators.…”

A panel of miRNAs derived from plasma extracellular vesicles as novel diagnostic biomarkers of lung adenocarcinoma

“…Several studies have confirmed that miR-451a, miR-194-5p, and miR-486-5p might inhibit tumor cell growth by suppressing proliferation and invasion or promote apoptosis by targeting cancer-associated genes [31][32][33][34][35]. Recently, some studies found that tumor suppressor gene-induced senescent cells modulate the immune response, which promotes the establishment of the inflammatory microenvironment that contributes to metastasis [36]. The abovementioned miRNAs might be secreted from tumor tissue and be involved in the immune escape of cancer cells, which contributes to tumor metastasis.…”