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. Author manuscript; available in PMC: 2020 Dec 18.
Published in final edited form as: Cancer Lett. 2019 Apr 8;454:1–13. doi: 10.1016/j.canlet.2019.04.001

Figure 6. Model showing contribution of CXCR6-CXCL16 axis in overcoming the effect of DTX:

Figure 6.

In response to DTX, prostate cancer cells up-regulate CXCR6, CXCL16 and ADAM-10, which also promotes CXCL16 cleavage. These changes together hyper-activate CXCR6-CXCL16 axis. TNFα, which could be regulated by ADAM-10 and CXCL16, leads to NF-κB activation by TRAFs (TNF-receptor associated factors) and NIK (NF-κB-inducing kinase). NIK also activates IKKα and Erk1/2. Activation of IKK complex leads to phosphorylation of IκB and enhances its proteasomal degradation. Free NF-κB subunits are then phosphorylated and translocate to the nucleus where they form homo- or heterodimers and increase cxcr6, cxcl16, and adam-10. Hyper-activated CXCR6-CXCL16 signaling a) supports epithelial to mesenchymal transition via Wnt/βcatenin pathway by affecting GSK3β activation and β-catenin stability and b) decreases apoptosis and enhances proliferation by affecting ERK1/2 activation, processing and trans-activation of NFκB resulting in over-expression of survivin as well as other anti-apoptotic and pro-survival molecules in concert with Stat3.