Senescence and tumor suppression [version 1; referees: 2 approved]

Abstract

Cellular senescence has emerged as a potent tumor suppression mechanism that restrains proliferation of cells at risk for malignant transformation. Although senescent cells have permanently exited the cell cycle, their presence can have detrimental effects on the surrounding tissue, largely due to the development of the senescence-associated secretory phenotype (SASP). Here, we review the tumor-suppressive and tumor-promoting consequences of the senescence response, focusing on the SASP as a key mediator of this dichotomy. Accumulating evidence suggests that the persistence of senescent cells can exacerbate the development of a pro-inflammatory, immunosuppressive microenvironment that can favor tumorigenesis. Given that senescence of tumor and stromal cells is a frequent outcome of anti-cancer therapy, approaches that harness the growth inhibitory effects of senescence while limiting its detrimental effects are likely to have great clinical potential.

Keywords

• Aging
• Cancer Therapeutics
• Cell Growth & Division
• Cell Signaling
• Control of Gene Expression
• Developmental Molecular Mechanisms
• Innate Immunity
• Leukocyte Signaling & Gene Expression
• Membranes & Sorting
• Nuclear Structure & Function
• Stem Cells & Regeneration