TY - JOUR
T1 - Senescence-Associated Secretory Phenotype as a Hinge Between Cardiovascular Diseases and Cancer
AU - Banerjee, Priyanka
AU - Kotla, Sivareddy
AU - Reddy Velatooru, Loka
AU - Abe, Rei J.
AU - Davis, Elizabeth A.
AU - Cooke, John P.
AU - Schadler, Keri
AU - Deswal, Anita
AU - Herrmann, Joerg
AU - Lin, Steven H.
AU - Abe, Jun Ichi
AU - Le, Nhat Tu
N1 - Funding Information:
The research activity related to this review was partially supported by grants from the National Institutes of Health (NIH) to JA (AI-156921).
Publisher Copyright:
Copyright © 2021 Banerjee, Kotla, Reddy Velatooru, Abe, Davis, Cooke, Schadler, Deswal, Herrmann, Lin, Abe and Le.
PY - 2021
Y1 - 2021
N2 - Overlapping risks for cancer and cardiovascular diseases (CVD), the two leading causes of mortality worldwide, suggest a shared biology between these diseases. The role of senescence in the development of cancer and CVD has been established. However, its role as the intersection between these diseases remains unclear. Senescence was originally characterized by an irreversible cell cycle arrest after a high number of divisions, namely replicative senescence (RS). However, it is becoming clear that senescence can also be instigated by cellular stress, so-called stress-induced premature senescence (SIPS). Telomere shortening is a hallmark of RS. The contribution of telomere DNA damage and subsequent DNA damage response/repair to SIPS has also been suggested. Although cellular senescence can mediate cell cycle arrest, senescent cells can also remain metabolically active and secrete cytokines, chemokines, growth factors, and reactive oxygen species (ROS), so-called senescence-associated secretory phenotype (SASP). The involvement of SASP in both cancer and CVD has been established. In patients with cancer or CVD, SASP is induced by various stressors including cancer treatments, pro-inflammatory cytokines, and ROS. Therefore, SASP can be the intersection between cancer and CVD. Importantly, the conventional concept of senescence as the mediator of cell cycle arrest has been challenged, as it was recently reported that chemotherapy-induced senescence can reprogram senescent cancer cells to acquire “stemness” (SAS: senescence-associated stemness). SAS allows senescent cancer cells to escape cell cycle arrest with strongly enhanced clonogenic growth capacity. SAS supports senescent cells to promote both cancer and CVD, particularly in highly stressful conditions such as cancer treatments, myocardial infarction, and heart failure. As therapeutic advances have increased overlapping risk factors for cancer and CVD, to further understand their interaction may provide better prevention, earlier detection, and safer treatment. Thus, it is critical to study the mechanisms by which these senescence pathways (SAS/SASP) are induced and regulated in both cancer and CVD.
AB - Overlapping risks for cancer and cardiovascular diseases (CVD), the two leading causes of mortality worldwide, suggest a shared biology between these diseases. The role of senescence in the development of cancer and CVD has been established. However, its role as the intersection between these diseases remains unclear. Senescence was originally characterized by an irreversible cell cycle arrest after a high number of divisions, namely replicative senescence (RS). However, it is becoming clear that senescence can also be instigated by cellular stress, so-called stress-induced premature senescence (SIPS). Telomere shortening is a hallmark of RS. The contribution of telomere DNA damage and subsequent DNA damage response/repair to SIPS has also been suggested. Although cellular senescence can mediate cell cycle arrest, senescent cells can also remain metabolically active and secrete cytokines, chemokines, growth factors, and reactive oxygen species (ROS), so-called senescence-associated secretory phenotype (SASP). The involvement of SASP in both cancer and CVD has been established. In patients with cancer or CVD, SASP is induced by various stressors including cancer treatments, pro-inflammatory cytokines, and ROS. Therefore, SASP can be the intersection between cancer and CVD. Importantly, the conventional concept of senescence as the mediator of cell cycle arrest has been challenged, as it was recently reported that chemotherapy-induced senescence can reprogram senescent cancer cells to acquire “stemness” (SAS: senescence-associated stemness). SAS allows senescent cancer cells to escape cell cycle arrest with strongly enhanced clonogenic growth capacity. SAS supports senescent cells to promote both cancer and CVD, particularly in highly stressful conditions such as cancer treatments, myocardial infarction, and heart failure. As therapeutic advances have increased overlapping risk factors for cancer and CVD, to further understand their interaction may provide better prevention, earlier detection, and safer treatment. Thus, it is critical to study the mechanisms by which these senescence pathways (SAS/SASP) are induced and regulated in both cancer and CVD.
KW - SASP
KW - cancer
KW - cardiovascular disease
KW - replicative senescence (RS)
KW - senescence associated secretory phenotype
KW - stress-induced premature senescence (SIPS)
UR - http://www.scopus.com/inward/record.url?scp=85157190624&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85157190624&partnerID=8YFLogxK
U2 - 10.3389/fcvm.2021.763930
DO - 10.3389/fcvm.2021.763930
M3 - Review article
AN - SCOPUS:85157190624
SN - 2297-055X
VL - 8
JO - Frontiers in cardiovascular medicine
JF - Frontiers in cardiovascular medicine
M1 - 763930
ER -