FIGURE 1.

The intrinsic and extrinsic mechanisms connecting cancer-associated adipocytes (CAAs) with senescence. Firstly, Autophagy activated by diverse intracellular and extracellular stress like hypoxia in CAAs is a hallmark of senescence as well as a tumor promoter. Furthermore, the secreted profile of CAAs is enriched in many of the same pro-inflammatory factors, such as IL-6, IL-8, and a variety of chemokines, which overlap strongly with the senescence-associated secretory phenotype (SASP). Finally, the activation of several oncogenes such as RAS or the loss of tumor suppressors like p53 can promote senescence. The senescent CAAs may arise from gap junctions and paracrine signals originating from tumor cells or other senescent cells. Ultimately, CAAs possessing multifarious senescent properties may enhance tumor angiogenesis, proliferation of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT).