Our finding that the inhibition of S1P1R signaling with an S1P antagonist suppressed the IL-22-evoked increase in breast cancer cell invasiveness by reducing MMP-9 activity (Figure 3) suggests that enhancement of the IL-22R1-S1PR1-linked axis via IL-22 stimulation may be involved in the increased metastatic potential of advanced breast cancer to bone niches (Figure 5C). This evidence concerns the gene MMP9 and breast carcinoma.