Hippo signaling pathway: A comprehensive gene expression profile analysis in breast cancer

Breast cancer (BC) is the most frequently diagnosed malignancy in women and a major public health concern. The Hippo pathway is an evolutionarily conserved signaling pathway that serves as a key regulator for a wide variety of biological processes. Hippo signaling has been shown to have both oncogenic and tumor-suppressive functions in various cancers. Core components of the Hippo pathway consist of various kinases and downstream effectors such as YAP/TAZ. In the current report, differential expression of Hippo pathway elements as well as the correlation of Hippo pathway mRNAs with various clinicopathologic characteristics, including molecular subtypes, receptor status, and methylation status, has been investigated in BC using METABRIC and TCGA datasets. In this review, we note deregulation of several Hippo signaling elements in BC patients. Moreover, we see examples of negative correlations between methylation of Hippo genes and mRNA expression. The expression of Hippo genes significantly varies between different receptor subgroups. Because of the clear associations between mRNA expression and methylation status, DNA methylation may be one of the mechanisms that regulate the Hippo pathway in BC cells. Differential expression of Hippo genes among various BC molecular subtypes suggests that Hippo signaling may function differently in different subtypes of BC. Our data also highlights an interesting link between Hippo components' transcription and ER negativity in BC. In conclusion, substantial deregulation of Hippo signaling components suggests an important role of these genes in breast cancer.