SMPD3 and breast cancer: After the orthotopic inoculation of these cell lines into mammary fat pad, we found that nSMase2 silencing in parental 4T1 breast cancer cells significantly decreased lung metastatic colonization (Fig. 1C), and in vivo imaging and histological observation revealed a significant decrease in the total number of metastatic nodules in nSMase2-knockdown lung tumors (Fig. 1D and supplemental Fig. 4A).