Senescence-Associated Secretory Phenotype as a Hinge Between Cardiovascular Diseases and Cancer.
Senescence-Associated Secretory Phenotype as a Hinge Between Cardiovascular Diseases and Cancer.
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DOI：
10.3389/fcvm.2021.763930
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发表时间：
2021
影响因子：
3.6
通讯作者：
Le NT
中科院分区：
文献类型：
--
作者：
Banerjee P;Kotla S;Reddy Velatooru L;Abe RJ;Davis EA;Cooke JP;Schadler K;Deswal A;Herrmann J;Lin SH;Abe JI;Le NT
全球两大死亡原因——癌症和心血管疾病（CVD）的风险重叠，表明这些疾病之间存在共同的生物学特征。衰老在癌症和心血管疾病发展中的作用已经确定。然而，其作为这些疾病之间的交叉点的作用仍不清楚。衰老最初的特征是大量分裂后不可逆的细胞周期停滞，即复制衰老（RS）。然而，越来越清楚的是，衰老也可能是由细胞应激引起的，即所谓的应激诱导的过早衰老（SIPS）。端粒缩短是 RS 的标志。端粒 DNA 损伤和随后的 DNA 损伤反应/修复对 SIPS 的贡献也已被提出。虽然细胞衰老可以介导细胞周期停滞，但衰老细胞也可以保持代谢活跃并分泌细胞因子、趋化因子、生长因子和活性氧（ROS），即所谓的衰老相关分泌表型（SASP）。 SASP 与癌症和 CVD 的关系已经确定。在患有癌症或 CVD 的患者中，SASP 是由各种应激源引起的，包括癌症治疗、促炎细胞因子和 ROS。因此，SASP 可以是癌症和 CVD 之间的交叉点。重要的是，衰老作为细胞周期停滞介质的传统概念受到了挑战，因为最近有报道称化疗诱导的衰老可以重新编程衰老的癌细胞以获得“干性”（SAS：衰老相关干性）。 SAS 使衰老癌细胞能够逃脱细胞周期停滞，并显着增强克隆生长能力。 SAS 支持衰老细胞促进癌症和 CVD，特别是在癌症治疗、心肌梗塞和心力衰竭等高压力条件下。随着治疗的进步增加了癌症和心血管疾病的重叠危险因素，进一步了解它们的相互作用可能会提供更好的预防、更早的检测和更安全的治疗。因此，研究癌症和心血管疾病中这些衰老途径 (SAS/SASP) 的诱导和调节机制至关重要。
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.
影响因子：
5.7
作者：
Mei Q;Li F;Quan H;Liu Y;Xu H
通讯作者：
Xu H