Research Paper Volume 13, Issue 3 pp 3290—3312
Suppression of p16 alleviates the senescence-associated secretory phenotype
- 1 Department of Pharmacology and Chemical Biology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
- 2 Biomedical Sciences Graduate Program, Penn State College of Medicine, Hershey, PA 17033, USA
Received: August 20, 2020 Accepted: January 21, 2021 Published: February 6, 2021https://doi.org/10.18632/aging.202640
How to Cite
Copyright: © 2021 Buj et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.