Moreover, our findings also showed that pharmacological blockage of individual signaling effectors of eNOS-NO-sGC-cGMP-PKG pathway or knockdown of eNOS could impair the stemness (spheroid growth capacity) of PCSCs and also inhibit the in vivo orthotopic tumor growth of prostate cancer cells, suggesting that targeting eNOS-NO-sGC-cGMP-PKG signaling may have therapeutic potential in PCSC targeting and also management of advanced prostate cancer. Here, NOS3 is linked to neoplasm.