肿瘤干细胞是乳腺癌术后复发的根源，其自我更新和多向分化潜能是导致乳腺癌复发和转移的关键。分泌蛋白LIPH调控乳腺癌干细胞的作用机制未明。我们在前期工作中发现复发转移的乳腺癌血清中LIPH表达明显高于无复发转移组，且与乳腺癌的不良预后显著相关。我们用LIPH蛋白孵育乳腺癌MDA-MB-231细胞后其增殖能力显著升高。通过外源性上调MDA-MB-231细胞的LIPH蛋白表达后，乳腺癌肿瘤干细胞的比率明显上调，且干细胞分化相关重要因子β-catennin核表达显著上调。因此，我们推测LIPH可能通过自分泌或胞浆高表达双重途径上调Wnt/β-catennin信号通路活性促进肿瘤干细胞的增殖和分化。为了证明这一假设，本研究以乳腺癌肿瘤干细胞和小鼠原位种植模型为研究对象，明确LIPH对乳腺癌肿瘤干细胞的增殖和分化功能的调控作用并阐明其调控机制，为进一步通过抑制LIPH控制乳腺癌的复发提供理论依据。

Cancer stem cells are considered to be the root of the recurrence and metastasis of breast cancer, and their self-renewal and multi-directional differentiation properties is the critical factor to cancer recurrence.The mechanisms of how secreted protein LIPH regulates breast cancer stem cells are unknown. In the preliminary work, it was found that the serum LIPH expression was significantly higher in the breast cancer patients with recurrence and metastasis compared to the cases without, and the LIPH protein expression was significantly related to the worse prognosis in clinical breast cancer patients. The proliferation and invasive ability of MDA-MB-231 cells was enhanced after cultured with LIPH protein in vitro. Moreover, exogenous expression of LIPH protein significantly increased the breast cancer stem cells ratio, companied with the up-regulated expression of nuclear β-catennin. Therefore, we speculate that LIPH may promote the proliferation and differentiation of cancer stem cells by up-regulating the activity of Wnt/β-catennin signaling pathway through autocrine or cytoplasmic expression. In order to prove this hypothesis, we intend to study the effect and mechanism of LIPH on the proliferation and differentiation of breast cancer stem cells in vitro and mouse situ implantation model in order to provide a theoretical basis for blocking recurrence and treatment of breast cancer.