NDR1 functions as tumor suppressor in glioblastoma by phosphoralation of YAP

Abstract Purpose: The NDR1(Nuclear Dbf2-related) kinase is a member of the NDR/LATS family which was a supplementary of Hippo pathway. However, whether NDR1 could inhibit glioblastoma (GBM) growth by phosphorylating YAP remains unknown. Meanwhile, the role of NDR1 in GBM was not clear. The purpose of this study was to investigate the role of NDR1-YAP pathway in GBM. Materials and Methods: Bioinformation analysis and immunohistochemistry was performed to identify the expression of NDR1 in GBM. The effect of NDR1 on cell proliferation and cell cycle was analyzed utilizing cck-8, clone formation, immunofluorescence and flow cytometry respectively. In addition, the xenograft tumor model was established as well. Protein interaction was examined by Co-ip and immunofluorescence. Results: Bioinformation analysis and immunohistochemistry of our petients’ tumor tissues showed that expression of NDR1 in tumor tissue was relatively lower than that in normal tissues and was positively related to lower survival rate. NDR1 could markedly reduce the proliferation, colony formation of U87 and U251. Furthermore, the results of flow cytometry showed that NDR1 led to cell cycle arrest at the G1 phase. Tumor growth was also inhibited in xenograft nude mouse models in NDR1-OE group. Western blotting and immunofluorescence showed that NDR1 could integrate with and phophoralate YAP at S127 site. Meanwhile, NDR1 could mediate apopptosis process. Conclusion: In summary, our findings pointed out that NDR1 functions as a tumor suppressor in GBM. NDR1 was identified as a novel regulator of YAP, which give us a in depth comprehension in Hippo signaling pathway.