Exploring the extensive crosstalk between the antagonistic cytokines- TGF-β and TNF-α in regulating cancer pathogenesis. (February 2021)

• Record Type: Journal Article
• Authors: Dash, Subhra; Sahu, Anirudha K.; Srivastava, Abhilasha; Chowdhury, Rajdeep; Mukherjee, Sudeshna
• Is Part Of: Cytokine. Volume 138(2021)
• Publication Date: 2021-02
• Subjects: EMT -- Autophagy -- Senescence -- Apoptosis -- Fibrogenesis -- TGF-β and TNF-α; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2020.155348
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: A plethora of cytokines produced in TME play a vital role in cancer prognosis. A contextual role of these pro-inflammatory cytokines in TME is key to migration. These cytokines majorly TGF-β and TNF-α in concert can have different roles. The review portrays the antagonistic role of these two cytokines in cancer prognosis. Abstract: 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-β) in cancer is controversially discussed in general inhibition of TGF-β promotes de novo tumorigenesis whereas paradoxically, TGF-β can promote malignancy in already established tumors. Another important cytokine, TNF-α have intense crosstalk with TGF-β from the fact that in a non-cancer context, TGF-β promotes fibrosis whereas TNF-α has anti-fibrotic activity. We have recently reported that TGF-β-induced differentiation of epithelial cells to mesenchymal type is suppressed by TNF-α through regulation of cellular homeostatic machinery- autophagy. Moreover, there are also rare reports of synergy between these two cytokines as well. The crosstalk between TGF-β and TNF-α 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-β and TNF-α control cancer prognosis.