Loss of DLG5 promotes breast cancer malignancy by inhibiting the Hippo signaling pathway.
Loss of DLG5 promotes breast cancer malignancy by inhibiting the Hippo signaling pathway.
复制标题
DLG5 缺失通过抑制 Hippo 信号通路促进乳腺癌恶性
DOI：
10.1038/srep42125
复制
发表时间：
2017-02-07
影响因子：
4.6
通讯作者：
Liu P
中科院分区：
文献类型：
--
作者：
Liu J;Li J;Li P;Wang Y;Liang Z;Jiang Y;Li J;Feng C;Wang R;Chen H;Zhou C;Zhang J;Yang J;Liu P
椎间盘大同源物5（DLG 5）在维持上皮细胞极性中起重要作用。最近的研究表明，DLG 5在过表达Yes相关蛋白（雅普）的细胞中减少。然而，DLG 5和雅普之间的确切关系尚不清楚。在这项研究中，我们发现DLG 5的缺失通过抑制Hippo信号通路和增加核雅普表达来促进乳腺癌细胞增殖。此外，DLG 5的耗竭诱导上皮-间充质转化（EMT）和破坏上皮细胞极性，这与Scribble，ZO 1，E-cadherin和N-cadherin的表达改变及其错误定位有关。有趣的是，我们首次报道了DLG 5的缺失抑制了Mst 1和Lats 1与Scribble的相互作用，这对雅普激活和TEA结构域（TEAD）家族成员的转录至关重要。总之，DLG 5表达的缺失通过使Hippo信号通路失活和增加核雅普而促进乳腺癌恶性。
Discs Large Homolog 5 (DLG5) plays an important role in the maintenance of epithelial cell polarity. Recent research showed that DLG5 is decreased in Yes-associated protein (YAP)-overexpressing cells. However, the exact relationship between DLG5 and YAP is not clear. In this study, we showed that loss of DLG5 promoted breast cancer cell proliferation by inhibiting the Hippo signaling pathway and increasing nuclear YAP expression. Furthermore, depletion of DLG5 induced epithelial-mesenchymal transition (EMT) and disrupted epithelial cell polarity, which was associated with altered expression of Scribble, ZO1, E-cadherin and N-cadherin and their mislocalization. Interestingly, we first reported that loss of DLG5 inhibited the interaction of Mst1 and Lats1 with Scribble, which was crucial for YAP activation and the transcription of TEA domain (TEAD) family members. In summary, loss of DLG5 expression promoted breast cancer malignancy by inactivating the Hippo signaling pathway and increasing nuclear YAP.