Loss of DLG5 promotes breast cancer malignancy by inhibiting the Hippo signaling pathway.
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.
Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Provincer, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Jie
J
Liu
Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Provincer, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Juan
J
Li
Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Provincer, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Pingping
P
Li
Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Provincer, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Yaochun
Y
Wang
Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Provincer, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Zheyong
Z
Liang
Department of Pathology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Yina
Y
Jiang
Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Provincer, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Jing
J
Li
Department of Oncology, the Shaanxi Provincial Corps' Hospital, Xi'an, Shaanxi, China.
Chen
C
Feng
Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Provincer, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Ruiqi
R
Wang
Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Provincer, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
He
H
Chen
Department of Breast Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Can
C
Zhou
Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York, USA.
Jianmin
J
Zhang
Department of Medical Oncology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Jin
J
Yang
Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.|Key Laboratory for Tumor Precision Medicine of Shaanxi Provincer, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Peijun
P
Liu
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D016764:Cell Polarity; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D000090683:Hippo Signaling Pathway; D006801:Humans; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D008819:Mice, Nude; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000091262:TEA Domain Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000091102:YAP-Signaling Proteins; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; C114461:DLG5 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C480591:SCRIB protein, human; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; C569042:TJP1 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D062826:Zonula Occludens-1 Protein; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor; C092745:LATS1 protein, human; D017346:Protein Serine-Threonine Kinases