Fig. 3

RKIP’s Downstream Targets. Red arrows depict the interactions of downstream gene products when RKIP expression is high and black arrows depict the interactions of downstream gene products when RKIP expression is low. 1: High expression of RKIP inhibits Raf, while low RKIP expression leads to Raf activation [15]; 2: Low RKIP is correlated with the epithelial to mesenchymal (EMT) transition [15]. Overexpression of Snail can inhibit RKIP and further induce EMT [81]; 3: RKIP overexpression sensitizes cells to TRAIL-mediated apoptosis [93]; 4: High expression of RKIP leads to inhibition of NF-κB, while low RKIP expression leads to high expression of NF-κB [15]; 5: TRAIL binds to its receptors, TRAIL-R1 and TRAIL-R2 [94]; 6: Upon binding to TRAIL-R1 or TRAIL-R2, TRAIL has been shown to stimulate activation of the NF-κB [94]; 7: TNF-α can stimulate TNFR-positive tumor cells [95]. TNF-α binds to its receptors, TNFR-1 and TNFR-2 [95]; 8: Upon stimulation of TNFR-positive tumor cells by TNF-α, cells can undergo activation of NF-κB [95]; 9: TNF-α can induce constitutive activation of NF-κB [63 via NF-kappaB and YY1’, in the regulation of tumor cell resistance to Fas-induced apoptosis]; 10: NF-κB mediates TNF-α- induced Bcl-6 expression [62]