在癌症进展中的上皮-间质转化（EMT）过程中，肿瘤细胞从E-钙粘蛋白（E-cadherin）转换为钙粘蛋白-11（CDH11），伴随着侵袭性和转移活性的增加。然而，CDH11影响肿瘤生长和转移的机制仍然不清楚。在这里，我们报告了CDH11在多种人类肿瘤中高表达，并且定位在细胞膜、细胞质和令人惊讶的是细胞核中。有趣的是，β-连接蛋白仍然与CDH11的羧基端的裂解产物（CTFs）结合，并且在绝大多数乳腺癌样本中与CTFs共定位在细胞核中。β-连接蛋白与CTFs的结合维持了β-连接蛋白的活性，而抑制CDH11的裂解导致β-连接蛋白磷酸化和Wnt信号的减弱，类似于CDH11缺失。我们的数据揭示了CDH11的先前未知作用，它在细胞质中稳定β-连接蛋白并促进其转位到细胞核，从而激活Wnt信号传导，进而增加增殖、迁移和侵袭潜力。本文受版权保护。保留所有权利。

During epithelial-mesenchymal transition (EMT) in cancer progression, tumor cells switch cadherin profile from E-cadherin to cadherin-11 (CDH11), which is accompanied by increased invasiveness and metastatic activity. However, the mechanism through which CDH11 may affect tumor growth and metastasis remains elusive. Here, we report that CDH11 was highly expressed in multiple human tumors and was localized on the membrane, in the cytoplasm and, surprisingly, also in the nucleus. Interestingly, β-catenin remained bound to carboxy-terminal fragments (CTFs) of CDH11, the products of CDH11 cleavage, and co-localized with CTFs in the nucleus in the majority of breast cancer samples. Binding of β-catenin to CTFs preserved β-catenin activity, whereas inhibiting CDH11 cleavage led to β-catenin phosphorylation and diminished Wnt signaling, similar to CDH11 knockout. Our data elucidates a previously unknown role of CDH11, which serves to stabilize β-catenin in the cytoplasm and facilitate its translocation to the nucleus, resulting in activation of Wnt signaling, with subsequent increased proliferation, migration and invasion potential.This article is protected by copyright. All rights reserved.