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Review
. 2021 Aug 12:9:722205.
doi: 10.3389/fcell.2021.722205. eCollection 2021.

The Paradoxical Role of Cellular Senescence in Cancer

Jing Yang  1   2 , Mengmeng Liu  1   2 , Dongchun Hong  1   2 , Musheng Zeng  2 , Xing Zhang  1
Affiliations
Review

The Paradoxical Role of Cellular Senescence in Cancer

Jing Yang et al. Front Cell Dev Biol. .

Erratum in

Abstract

Cellular senescence occurs in proliferating cells as a consequence of various triggers including telomere shortening, DNA damage, and inappropriate expression of oncogenes. The senescent state is accompanied by failure to reenter the cell cycle under mitotic stimulation, resistance to cell death and enhanced secretory phenotype. A growing number of studies have convincingly demonstrated a paradoxical role for spontaneous senescence and therapy-induced senescence (TIS), that senescence may involve both cancer prevention and cancer aggressiveness. Cellular senescence was initially described as a physiological suppressor mechanism of tumor cells, because cancer development requires cell proliferation. However, there is growing evidence that senescent cells may contribute to oncogenesis, partly in a senescence-associated secretory phenotype (SASP)-dependent manner. On the one hand, SASP prevents cell division and promotes immune clearance of damaged cells, thereby avoiding tumor development. On the other hand, SASP contributes to tumor progression and relapse through creating an immunosuppressive environment. In this review, we performed a review to summarize both bright and dark sides of senescence in cancer, and the strategies to handle senescence in cancer therapy were also discussed.

Keywords: aging; cancer; senescence; senescence-associated secretory phenotype; senescent cell.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Triggers and main effector pathways of senescence. Persistent DNA damage induced by diverse stimuli and abnormal oncogenic signal lead to senescence mainly by regulating p16INK4a–pRb and p53/p21 pathways.
FIGURE 2
FIGURE 2
Triggers of senescence, characteristics of senescent cells, and components of senescence-induced secretory phenotype (SASP).
FIGURE 3
FIGURE 3
The role of senescence in cancer. SASP components induce or enhance the senescent-associated growth arrest in autocrine and paracrine manners, thereby inhibiting cancer progression. In addition to reinforcing senescence, SASP can also activate immune surveillance, which is orchestrated by specific immune responses mediated by antigen-specific CD4 (+) T cells. SASP also recruits natural killer (NK) cells and alters macrophage polarization to eliminate senescent tumor cells and suppress tumorigenesis. By contrast, senescent cells and SASP components can directly or indirectly promote tumor cells growth, invasion and metastasis by promoting tumor vascularization, maintaining stem-cell features, creating an immunosuppressive environment, remodeling tissue structure, inducing drug resistance, and stimulating epithelial-mesenchymal transition (EMT).
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