Fig. 1.

The role of TNF-α and IL-6 in cancer progression. The Covid-19 infection initiates the cytokine storm, characterized by the excessive production of pro-inflammatory cytokines. IL-6 receptor binding results in the activation of JAK/STAT3 signaling. JAK mediates the activation of the Ras/Raf/MEK signaling cascade. Furthermore, JAK activates the PI3K/Akt signaling pathway, which activates NFκβ. NFκβ translocate to the nucleus where it promotes the expression of gene products responsible for tumourigenesis. STAT3 activation results in dimer formation which translocate to the nucleus where it mediates gene expression. STAT3 also promotes cell survival by activating the anti-apoptotic proteins Bcl-2 and Bcl-XL. TNFR binding activates the effector proteins FADD, TRADD, RIP, TRAF2, MEKK1, Ask1 and pro-caspase-8. This results in the activation of NFκβ and the activation of the AP-1 protein through MEKK1/4, MKK4/7 and MAPK signaling. Collectively, the activation of MAPK, NFκβ, STAT3 dimerisation and Ap-1 promotes the expression of target genes that promotes cancer proliferation, survival, angiogenesis, metastasis and inflammation.