Here, we carry out analyses of GD2 expression in prostate cancer patient tissues and their metastases as well as in cell line models of CRPC progression and use CRISPR-KO of GD3S in human and murine CRPC cell line models to establish that GD2 expression is a feature of a small fraction of tumor cells enriched in tumorsphere growth in vitro, and that GD3S is required for tumorigenesis in CRPC. Here, ST8SIA1 is linked to prostate cancer.