当前复发、转移乳腺癌患者的临床治疗预后极差，研究表明靶向清除乳腺肿瘤干细胞是改善这一临床困局的有效策略。我们前期的研究表明脂肪酸合成酶(Fatty acid Synthase, FASN)通过调控Wnt/β-catenin信号通路在驱动、增强、维持乳腺肿瘤细胞干性过程扮演重要角色，而质子泵抑制剂(Proton pump inhibitors, PPIs)是FASN的有效抑制剂，可以体外显著抑制乳腺癌细胞FASN全酶活性，并显著抑制乳腺癌细胞干性。基于此，我们拟进一步通过乳腺癌细胞、动物模型探究、阐释FASN介导Wnt3a棕榈酰化修饰激活Wnt/β-catenin信号通路促乳腺癌细胞干性和PPIs靶向FASN抑制Wnt3a棕榈酰化修饰及下游信号通路对乳腺肿瘤干细胞的清除作用与机制，以期为PPIs“老药新用”于改善复发、转移乳腺癌患者的临床治疗预后提供临床试验和用药依据。

Currently, the recurrent or metastatic breast cancer type is with very poor prognosis in clinical. The recent studies show that targeting to eradicate breast cancer stem cells (BCSCs) is an effective treatment for improving the clinical dilemma. Our previous studies revealed that fatty acid synthase (FASN) could drive, enhance and maintain stemness of breast cancer cells via regulating Wnt/β-catenin signal pathway and proton pump inhibitors (PPIs) with significant inhibition of FASN holoenzyme activity has a remarkable elimination of breast cancer cells’ stemness. Based on the above, we would like to further explore and interpret the effects and mechanisms of FASN promotes BCSCs-like properties via mediating palmitoylation of Wnt3a to activate Wnt/β-catenin signal pathway and PPIs target FASN to inhibit palmitoylation of Wnt3a and its downstream signal pathway to eradicate BCSCs, in order to provide clinical trails and drug usage evidences for repurposing PPIs to improve the recurrent or metastatic breast cancer patients’ current poor clinical prognosis.