转移与复发是乳腺癌病人死亡的主要原因，Wnt信号通路失调是乳腺癌转移的重要原因之一。前期我们已发表文章报道细胞核内BRMS1-L通过表观遗传机制调控Wnt信号通路受体FZD10的表达抑制乳腺癌的转移。近期预实验我们发现：1. 核外BRMS1-L与Wnt分泌调节蛋白WLS相互作用；2. BRMS1-L降低WLS的稳定性；3. BRMS1-L降低WLS的乙酰化水平。据此我们提出假设：一方面核内BRMS1-L表观调控Wnt受体FZD10的表达，抑制Wnt通路(前期发表结果)；另一方面，核外BRMS1-L通过降低WLS的乙酰化水平促进WLS的降解，抑制Wnt的分泌，从而抑制Wnt信号通路。核内与核外BRMS1-L通过不同机制共同调控Wnt信号通路，抑制乳腺癌转移。本项目中，我们将深入探讨BRMS1-L调控WLS稳定性的机制，以及BRMS1-L与WLS表达水平在乳腺癌中的相关性及临床意义。

Metastasis is the major cause leading to the death of breast cancer patients. Dysregulation of Wnt signaling pathway often results in breast cancer metastasis. We previously revealed that nuclear BRMS1-L epigenetically suppressed FZD10 expression and repressed the metastasis of breast cancer. In this study, we identified another BRMS1-L interacting protein WLS, a Wnt secretion helper protein using TAP-MS. In addition, we found that BRMS1-L reduced the acetylation level of WLS and promoted the degradation of WLS. Based on these results, we hypothesize that BRMS1-L suppresses the Wnt/β-Catenin signalling pathway throuth two manner. In one hand, BRMS1-L epigenetically represses Wnt receptor FZD10 expressio, on the other hand, BRMS1-L posttransationally regulates the stability of Wnt secretion helper protein WLS. We will further reveal the mechanisms by which BRMS1-L promotes WLS degradation. In addition, we will investigate its clinical significance of the interaction between BRMS1-L and WLS in breast cancer metastasis.