Expression and significance of Hippo/YAP signaling in glioma progression

Abstract

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.

Keywords: Expression; Glioma; Hippo pathway; LATS1/2; TAZ; YAP1.