Expression and significance of Hippo/YAP signaling in glioma progression
- 688 Downloads
Dysregulation of Hippo/YAP signaling leads to aberrant cell growth and neoplasia. Although the roles and regulation of Hippo/YAP signaling were extensively studied in cancer biology recently, study systematically checking the expression pattern of core components of this pathway at the tumor tissue level remains lacking. In this study, we thoroughly examined the profile of core components of Hippo/YAP signaling in patient specimens both at the mRNA and at protein levels. We found that the mRNA level of YAP1/TAZ and their target genes, CRY61, CTGF, and BIRC5, was remarkably amplified in glioma tissues. Consistently, the protein level of YAP1/TAZ increased and meanwhile those of p-YAP1/p-TAZ and LATS1/2 decreased in gliomas. Unexpectedly, both the mRNA and protein levels of MST1/2 increased in the glioma tissues, inconsistent with its presumed tumor suppressor identity. In addition, over-expression of LATS2 decreased, while over-expression of YPA1 increased the cell proliferation ability. Furthermore, based on the data from the free public database, YAP1/TAZ and BIRC5 were positively associated with the prognosis of glioma patients, while LATS1/2 exhibited negative correlation with the glioma patient prognosis. Collectively, we deduce that, in glioma tissue context, MST1/2 may not be the essential component of the hippo/YAP pathway. Moreover, our findings uncover a new evidence supporting that YAP1/TAZ-BIRC5 might be abnormally activated due to LATS1/2 down-regulation, which in turn promote the occurrence and development of gliomas, paving the way to identify the potential therapeutic molecular target for gliomas.
KeywordsGlioma Hippo pathway LATS1/2 YAP1 TAZ Expression
The research was supported by National Natural Science Foundation of China (No.81372699; No. 81472345), 333 talent project of Jiangsu Province (No. BRA2015394), and six major talent summit of Jiangsu Province (No. WSW-039). We thank Dr. B Zhao at Life Sciences Institute and Innovation Center for Cell Signaling Network, Zhejiang University for Flag-LATS2 and Flag-YAP1 plasmids.
Compliance with ethical standards
Conflicts of interest
- 8.Li W, Cooper J, Zhou L, Yang C, Erdjument-Bromage H, Zagzag D, Snuderl M, Ladanyi M, Hanemann CO, Zhou P, Karajannis Matthias A, Giancotti Filippo G. Merlin/nf2 loss-driven tumorigenesis linked to crl4dcaf1-mediated inhibition of the hippo pathway kinases lats1 and 2 in the nucleus. Cancer Cell. 2014;26:48–60.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Lau AN, Curtis SJ, Fillmore CM, Rowbotham SP, Mohseni M, Wagner DE, Beede AM, Montoro DT, Sinkevicius KW, Walton ZE, Barrios J, Weiss DJ, Camargo FD, Wong KK, Kim CF. Tumor-propagating cells and yap/taz activity contribute to lung tumor progression and metastasis. EMBO J. 2014;33:468–81.CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Takahashi Y, Miyoshi Y, Takahata C, Irahara N, Taguchi T, Tamaki Y, Noguchi S. Down-regulation of lats1 and lats2 mrna expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers. Clin Cancer Res: Off J Am Assoc Cancer Res. 2005;11:1380–5.CrossRefGoogle Scholar
- 27.Cordenonsi M, Zanconato F, Azzolin L, Forcato M, Rosato A, Frasson C, Inui M, Montagner M, Parenti AR, Poletti A, Daidone MG, Dupont S, Basso G, Bicciato S, Piccolo S. The hippo transducer taz confers cancer stem cell-related traits on breast cancer cells. Cell. 2011;147:759–72.CrossRefPubMedGoogle Scholar
- 38.Tang F, Gill J, Ficht X, Barthlott T, Cornils H, Schmitz-Rohmer D, Hynx D, Zhou D, Zhang L, Xue G, Grzmil M, Yang Z, Hergovich A, Hollaender GA, Stein JV, Hemmings BA, Matthias P. The kinases ndr1/2 act downstream of the hippo homolog mst1 to mediate both egress of thymocytes from the thymus and lymphocyte motility. Sci Signal. 2015;8:ra100.CrossRefPubMedGoogle Scholar