Open AccessSuppression of p16 alleviates the senescence-associated secretory phenotype
Author(s) -
Raquel Buj,
Kelly E. Leon,
Marlyn A Anguelov,
Katherine M. Aird
Publication year - 2021
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.202640
Subject(s) - senescence , carcinogenesis , phenotype , cell cycle , cell cycle checkpoint , context (archaeology) , biology , microbiology and biotechnology , gene knockdown , proinflammatory cytokine , secretion , dna damage , tumor microenvironment , oncogene , cancer research , cell , cell culture , cancer , gene , immunology , genetics , inflammation , endocrinology , dna , paleontology
Oncogene-induced senescence (OIS) is characterized by increased expression of the cell cycle inhibitor p16, leading to a hallmark cell cycle arrest. Suppression of p16 in this context drives proliferation, senescence bypass, and contributes to tumorigenesis. OIS cells are also characterized by the expression and secretion of a widely variable group of factors collectively termed the senescence-associated secretory phenotype (SASP). The SASP can be both beneficial and detrimental and affects the microenvironment in a highly context-dependent manner. The relationship between p16 suppression and the SASP remains unclear. Here, we show that knockdown of p16 decreases expression of the SASP factors and pro-inflammatory cytokines IL6 and CXCL8 in multiple models, including OIS and DNA damage-induced senescence. Notably, this is uncoupled from the senescence-associated cell cycle arrest. Moreover, low p16 expression in both cancer cell lines and patient samples correspond to decreased SASP gene expression, suggesting this is a universal effect of loss of p16 expression. Together, our data suggest that p16 regulates SASP gene expression, which has implications for understanding how p16 modulates both the senescent and tumor microenvironment.