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A schematic illustrating a TIMP-1/CD63/ITGB1/P-STAT3 positive feedback loop as suggested by the results presented above. Exposed to CAF-CM-derived TIMP-1, BC cells are stimulated to activate STAT3 and to produce more TIMP-1, which then leads to further STAT3 activation. In addition, IL-6 secreted by CAFs helps to maintain STAT3 activation, thereby fueling the feedback loop. IL-6R = IL-6 receptor, gp130 = glycoprotein 130, JAK1 = Janus kinase 1.
