The CXCL8-CXCR1/2 pathways in cancer

- CXCL8-CXCR1/2 axis activates multiple intracellular signaling pathways which regulate proliferation and differentiation of cells.
- CXCL8 acts as an important multifunctional cytokine to modulate proliferation, invasion and migration of tumor cells and induced tumor immunosuppression via an autocrine or paracrine manner.
- CXCL8-CXCR1/2 axis mediates initiation and progression of multiple cancers and is associated with early relapse and poor prognosis.
- CXCL8-CXCR1/2 axis is potential to be applied as a cancer therapeutic target.

Persistent infection or chronic inflammation contributes significantly to tumourigenesis and tumour progression. C-X-C motif ligand 8 (CXCL8) is a chemokine that acts as an important multifunctional cytokine to modulate tumour proliferation, invasion and migration in an autocrine or paracrine manner. Studies have suggested that CXCL8 and its cognate receptors, C-X-C chemokine receptor 1 (CXCR1) and C-X-C chemokine receptor 2 (CXCR2), mediate the initiation and development of various cancers including breast cancer, prostate cancer, lung cancer, colorectal carcinoma and melanoma. CXCL8 also integrates with multiple intracellular signalling pathways to produce coordinated effects. Neovascularisation, which provides a basis for fostering tumour growth and metastasis, is now recognised as a critical function of CXCL8 in the tumour microenvironment. In this review, we summarize the biological functions and clinical significance of the CXCL8 signalling axis in cancer. We also propose that CXCL8 may be a potential therapeutic target for cancer treatment.

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