Exploring the extensive crosstalk between the antagonistic cytokines- TGF-β and TNF-α in regulating cancer pathogenesis

A plethora of cytokines are produced in the tumor microenvironment (TME) those play a vital role in cancer prognosis. Though it is completely contextual, cytokines produced from an inflammatory micro-environment can either modulate cancer progression at early stages of tumor development or in later stages cytokine derived cues can in turn control tumor cell invasion and metastasis. Therefore, understanding the crosstalk between the key cytokines regulating cancer prognosis is critical for the development of an effective therapy. In this regard, the role of transforming growth factor-beta (TGF-alpha) in cancer is controversially discussed in general inhibition of TGF-beta promotes de novo tumorigenesis whereas paradoxically, TGF-beta can promote malignancy in already established tumors. Another important cytokine, TNF-alpha have intense crosstalk with TGF-beta from the fact that in a non-cancer context, TGF-beta promotes fibrosis whereas TNF-alpha has anti-fibrotic activity. We have recently reported that TGF-beta-induced differentiation of epithelial cells to mesenchymal type is suppressed by TNF-alpha through regulation of cellular homeostatic machineryautophagy. Moreover, there are also rare reports of synergy between these two cytokines as well. The crosstalk between TGF-beta and TNF-alpha is not only limited to regulating cancer cell differentiation and proliferation but also includes involvement in cell death. In this review, we hence summarize the molecular mechanisms by which these two important cytokines, TGF-beta and TNF-alpha control cancer prognosis.

Automated summary

Cytokines produced in the tumor microenvironment play a crucial role in cancer prognosis, with the interplay between TGF-beta and TNF-alpha being particularly important for understanding tumor development and progression.