The present study shows that silencing the choline-producing glycerophosphodiesterase EDI3 alters intracellular levels of key glycerophospholipids, reduces colony formation, cell adhesion, and anoikis-resistance in vitro, as well as decreases the metastatic burden in two experimental metastasis models of ER-HER2+ breast cancer in vivo. Here, ESR1 is linked to breast cancer.