Abstract B17: Hyperactivating the Hippo pathway effector TAZ distorts the immune microenvironment in promoting the mesenchymal transformation in glioblastoma

Abstract

Abstract Glioblastoma (GBM), the deadliest and most common primary brain malignancy in adults, is highly heterogeneous with variable prognoses and treatment responses. The mesenchymal subtype of GBM is associated with the worst prognosis and highest treatment resistance. It is still not clear how GBM mesenchymal differentiation is achieved. Hyperactivity of transcriptional coactivator with PDZ-binding motif (TAZ) was linked to the GBM mesenchymal transformation, although its role in this process remains unclear. Here, by using orthotopic xenograft mouse GBM models, we found that hyperactive TAZ in tumor cells promotes myeloid cells to infiltrate into tumors. Such enhanced myeloid cell infiltration is associated with the mesenchymal transformation and tumor progression. We demonstrated that these TAZ-induced tumorigenic properties rely on its interaction with the transcription factor, TEA domain family member (TEAD). Such interaction induces the transcription of chemokines that are able to recruit the myeloid cells. Specific depletion of the infiltrated myeloid cells is able to slow down the tumor progression. Our studies suggested that recruiting myeloid cells by hyperactive TAZ contributes the mesenchymal transformation and tumor progression in glioblastoma. Citation Format: Patricia Yee, Yiju Wei, Zhijun Liu, Wei Li. Hyperactivating the Hippo pathway effector TAZ distorts the immune microenvironment in promoting the mesenchymal transformation in glioblastoma [abstract]. In: Proceedings of the AACR Special Conference on the Hippo Pathway: Signaling, Cancer, and Beyond; 2019 May 8-11; San Diego, CA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(8_Suppl):Abstract nr B17.