CXCR4 is a Gi-coupled chemokine receptor involved in chemotaxis
(directed migration) of tumor and stromal cells into the primary tumor and the prometastatic
niche that are enriched in CXCL12. In breast cancer, cell surface CXCR4
levels and activity are upregulated and play an important role in local invasion and
metastasis. During cancer progression, the CXCL12-CXCR4 axis orchestrates
infiltration of endothelial cells and a variety of leukocytes to drive an immunosuppressive
tumor microenvironment (TME). When CXCL12 from the TME activates
plasma membrane-resident CXCR4 in tumor and stromal cells, a variety of pathways
are activated involving signaling modules such as PI3K-AKT, MEK-ERK, and c-Sr-
-p130CAS-paxillin. This triggers a wide variety of cellular processes that drive breast
cancer progression, chemoresistance, and metastasis. This provides an opportunity to
intervene and target these signaling axes or nodes in clinical trials to antagonize tumor
growth metastasis. Finally, careful selection of targeted therapies in combination with
the standard of care therapy should be selected judiciously for each patient (precision
medicine) with the aim of improving the longevity with minimal toxicity to metastatic
breast cancer patients.
Keywords: Breast Cancer, CXCR4, Metastasis, Signaling, Tumor Progression.
