Article Figures & Data
Figures
- Figure 1
The dual roles of senescent cells in tumor development and progression. The occurrence of aging or therapeutic senescence has dual effects on tumor development and treatment. On the one hand, aging-mediated tumor cell growth arrest functions primarily as a tumor suppressor in early stages of tumor progression. Moreover, components secreted by senescent cells such as IL-6 and IL-8 reinforce the effects of senescence and further inhibit tumor progression (blue arrow). On the other hand, aging of the whole body mediates changes in the tumor environment, thereby aggravating tumor treatment resistance, tumor metastasis, angiogenesis, downstream metastasis, and early remodeling of the micro-environment (red arrow). Notably, senescent fibroblasts secrete components such as IL-6, L-8, AREG, CCL5, CXCL12, OPN, and HGF, which promote tumor cell proliferation, metastasis, and angiogenesis by remodeling the tumor microenvironment through MMPs and VEGF. In metastatic sites, senescent osteoblasts remodel the downstream metastatic microenvironment and promote the seeding and proliferation of circulating tumor cells.
- Figure 2
Cell-fate decisions mediated by intricate molecular crosstalk. At the cellular and molecular levels, multiple signaling pathways and regulatory mechanisms are intertwined in a complex network. Dysregulated signaling cascades, such as the p53-p21 and p16INK4a-Rb pathways, lead to imbalances in the cellular senescence response to various stresses, thereby contributing to malignant transformation. Certain mutations have been shown to delay the aging process but also increase the risk of tumorigenesis. In the process of malignant transformation, cellular homeostasis maintenance mechanisms and epigenetic reprogramming play important roles. The maintenance mechanism of cellular homeostasis is not only key to maintaining biological homeostasis but also serves as barrier to preventing the malignant transformation of cells. However, cancer cells achieve aberrant proliferation and survival by exploiting the vulnerabilities of the aging machinery and escaping the restrictions of the maintenance mechanisms of cellular homeostasis. In addition, senescent cells alter the tumor microenvironment by secreting proinflammatory factors, which further contribute to tumor development and treatment resistance.
- Figure 3
Senescence-based anti-tumor strategies. Inducing the senescence of tumor cells at early stages of tumor development is an effective anti-tumor concept. In late tumor stages, immunosuppression of the microenvironment and various treatment resistance elements are usually alleviated by elimination of senescent cells. Combined multi-disciplinary, multi-omics analyses using multiple technical methods are expected to reveal the intricate relationship between cellular senescence and tumor malignant transformation, and lead to more efficient tumor treatments in the future.
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