2c). Finally, we performed gene knockdown experiments. RANK knockdown induced a decrease in cell viability in the HAMON cells, not in the HUVECs (Fig. 2d-g). Mechanistically, knockdown of RANK suppressed the phosphorylation of Erk (Fig. 2f). In various cancers, positive associations between RANK-RANKL signalling and tumour development have been reported. 6 Recent clinical trials in lung cancer have shown that denosumab could reduce the risk of skeletal-related events and improve overall survival more than zoledronic acid. 7,8 Also, the RANK-RANKL signalling pathway is known to be involved in cancer cell migration and angiogenesis. 6 Jones et al. 9 demonstrated that the migration of RANK-expressing cancer cells was accelerated by RANKL, which is reported to be involved in the MAP kinase pathways. 6 Further, RANK-RANKL signalling pathways stimulate angiogenesis through an Src and phospholipase C-mechanism. 10 The results of the present and previous studies suggest that RANK-RANKL pathways highly contribute to angiogenesis and cell proliferation in CAS cells (Fig. 2h). In conclusion, we have reported a case of CAS with metastases in the sternum and liver which have remained stable through denosumab therapy. Also, we demonstrated that the RANK/ RANK pathway is activated in CAS. Our data suggest that the inhibition of RANK-RANKL signalling could be a potential treatment option for CAS.

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