The functional multipotency of transforming growth factor β signaling at the intersection of senescence and cancer

The transforming growth factor beta (TGF-beta) family of cytokines comprises a group of proteins, their receptors, and effector molecules that, in a coordinated manner, modulate a plethora of physiological and pathophysiological processes. TGF-beta 1 is the best known and plausibly most active representative of this group. It acts as an immunosuppressant, contributes to extracellular matrix remodeling, and stimulates tissue fibrosis, differentiation, angiogenesis, and epithelial-mesenchymal transition. In recent years, this cytokine has been established as a vital regulator of organismal aging and cellular senescence. Finally, the role of TGF-beta 1 in cancer progression is no longer in question. Because this protein is involved in so many, often overlapping phenomena, the question arises whether it can be considered a molecular bridge linking some of these phenomena together and governing their reciprocal interactions. In this study, we reviewed the literature from the perspective of the role of various TGF-beta family members as regulators of a complex mutual interplay between senescence and cancer. These aspects are then considered in a broader context of remaining TGF-beta-related functions and coexisting processes. The main narrative axis in this work is centered around the interaction between the senescence of normal peritoneal cells and ovarian cancer cells. The discussion also includes examples of TGF-beta activity at the interface of other normal and cancer cell types.

Automated summary

The transforming growth factor beta (TGF-beta) family of cytokines plays a crucial role in regulating various physiological and pathophysiological processes, including immune suppression, tissue remodeling, and cancer progression. TGF-beta 1, in particular, is a well-known and highly active member of this family. It is involved in modulating aging, cellular senescence, and their interaction with cancer. This study reviewed the literature on the role of different TGF-beta family members in the complex interplay between senescence and cancer, highlighting the interaction between normal peritoneal cells and ovarian cancer cells as a central focus. Examples of TGF-beta activity in other normal and cancer cell types were also discussed.