Fig. 6

S6 inhibits bone metastasis of breast cancer cells and tumors. A ALP staining of osteoblast differentiation after S6 (2 µM) treatment for 14 days. B ARS staining of osteoblast differentiation after S6 (2 µM) treatment for 21 days. C Typical X-ray and microCT images of bone metastases in nude mice inoculated with SCP2 and treated with DMSO or S6 (10 mg/kg). D H&E and TRAP staining images of bone metastases in nude mice inoculated with SCP2 and treated with DMSO or S6. E Transwell migration assays revealed that treatment with S6 or AMD3100 (a CXCR4 inhibitor) inhibited SCP2 cell migration towards MC3T3-E1 cells. F treatment with S6 reduced the levels of CXCL12 in the supernatants of co-cultured SCP2 and MC3T3-E1 cells. G Bioluminescence imaging analysis of bone metastases in nude mice 5 weeks after intraventricular injection with SCP2 cells and treatment with DMSO or S6 (n = 8–10 per group). H A schematic diagram reveals that SOST binding to STAT3 activates the RAS and TGF-β/SMAD/CXCR4 signaling to promote cancer cell proliferation and osteotrophy, while S6 inhibits the SOST-STAT3 binding to inhibit the subsequent process