SASP: Tumor Suppressor or Promoter? Yes!

Abstract

Cellular senescence is a permanent growth arrest in cells with damage or stress that could lead to transformation. Some tumor cells also undergo senescence in response to chemotherapy. Senescent cells secrete cytokines and other factors of the senescence-associated secretory phenotype (SASP) that contribute to tumor suppression by enforcing arrest and recruiting immune cells that remove these damaged or oncogene-expressing cells from organisms. However, some cells can develop a SASP comprising factors that are immunosuppressive and protumorigenic by paracrine mechanisms. Likewise, the SASP in treated cancers can either contribute to durable responses or drive relapse. Here, we discuss the studies that have demonstrated a complex and often conflicting role for the SASP in tumorigenesis and treatment response.

Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival

“…Further research using human patient samples and mouse models has demonstrated that p53 wild-type breast tumors respond to chemotherapy by entering cell cycle arrest and senescence with concomitant expression of cytokines and chemokines of the senescence-associated secretory phenotype (SASP; te Poele et al, 2002; Jackson et al, 2012; Tonnessen-Murray et al, 2018). The SASP can promote tumorigenic properties such as proliferation, survival, stemness, immune evasion, and metastasis (Rodier et al, 2009; Achuthan et al, 2011; Cahu et al, 2012; Canino et al, 2012; Toso et al, 2014; Rao and Jackson, 2016).…”

Role of the Gut–Liver Axis in Liver Inflammation, Fibrosis, and Cancer: A Special Focus on the Gut Microbiota Relationship

“…We also demonstrated the susceptibility of cygb ‐knockout mice to develop liver cancer when treated with diethylnitrosamine or a choline‐deficient L‐amino acid‐defined diet, implicating the regulatory role of CYGB in HSCs for the development of the tumor microenvironment . In addition, senescent HSCs showing the senescence‐associated secretory phenotype (SASP) produce a variety of secreted proteins, such as cytokines, chemokines, and proteases, that promote liver tumor progression and are present in an obesity‐associated liver tumor microenvironment (Fig. ).…”

Membrane metallo‐endopeptidase mediates cellular senescence induced by oncogenic PIK3CAH1047R accompanied with pro‐tumorigenic secretome

“…These factors have been reported to be important components of SASP. 33 IL-6 is a pleiotropic factor, which elicits a wide spectrum of physiological and pathogenic events such as cell proliferation. 34 Indeed, IL-6 promoted the proliferation of serum-depleted MCF-10A cells in a dose-dependent manner, while neutralization of IL-6 by specific antibody abrogated this effect (Fig.…”