2. Academic Validation
  3. 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

  • Sci Rep. 2017 Feb 7;7:42125. doi: 10.1038/srep42125.
Jie Liu 1 2,  Juan Li 1 2,  Pingping Li 1 2,  Yaochun Wang 1 2,  Zheyong Liang 1 2,  Yina Jiang 3,  Jing Li 1 2,  Chen Feng 4,  Ruiqi Wang 1 2,  He Chen 1 2,  Can Zhou 5,  Jianmin Zhang 6,  Jin Yang 7,  Peijun Liu 1 2
Affiliations

Affiliations

  • 1 Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • 2 Key Laboratory for Tumor Precision Medicine of Shaanxi Provincer, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • 3 Department of Pathology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • 4 Department of Oncology, the Shaanxi Provincial Corps' Hospital, Xi'an, Shaanxi, China.
  • 5 Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
  • 6 Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York, USA.
  • 7 Department of Medical Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
PMID: 28169360 DOI: 10.1038/srep42125
Abstract

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.

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