The HIPPO signaling pathway and its transcriptional coregulators, YAP and TAZ, have recently arisen as major determining factors of malignancy in many cancers. When this pathway is inactive, YAP and TAZ translocate in the nucleus, where they can regulate the transcription factors’ activity. In the tumor microenvironment, signals such as inflammation and oncogenic signaling allow the end of the YAP/TAZ’s inhibition, promoting their nuclear translocation. Then, these two factors can play the role of coactivators through their interaction with various transcription factors, including the TEAD family members. The transcriptional complex YAP/TAZ/TEAD1-4 enhances the transcription of target genes involved in some processes as cell proliferation, invasion, and angiogenesis, required for solid tumor progression.
Our research about this signaling pathway showed the influence of the YAP cofactor expression on the prognosis of patients with glioma and its role in cell proliferation of glioblastoma stem cells (GSC). Also, there are little data about the regulation of HIPPO signaling via membrane receptors, tyrosine kinases, and/or G protein-coupled receptors. We demonstrated its regulation in GSC by the EGFR-PTEN-AKT signaling axis that is dependent on the mutational status of PTEN. Thenceforth, our present research works focus on:
the characterization of the mosaic of HIPPO signaling effectors and their prognosis value,
their role in the processes involved in tumor progression,
the regulation of the HIPPO signaling pathway, particularly by receptors altered in gliomas,
the development of organoid models relevant to studying this pathway.
