Abstract 3349: TEAD4 expression in human hepatocellular carcinoma correlates with poor prognosis and promotes tumor growth and migration

Abstract

Abstract Background: TEAD family is a group of four transcription factor members, including TEAD1, TEAD2, TEAD3 and TEAD4. These genes are known to be involved in the regulation of different genes associated with cell proliferation, differentiation and apoptosis. TEAD proteins represent the major downstream effectors of the conserved Hippo signalling pathway, known to be deregulated in different cancer entities. In the present study, we sought to explore the expression of TEAD4 in hepatocellular carcinoma (HCC) and its effect in in vitro models. Methods: We evaluated TEAD4 expression at mRNA level using data from The Cancer Genome Atlas (liver dataset) and at protein level using a tissue microarray containing 192 HCCs, 108 cirrhotic tissues and 79 normal liver samples. For in vitro experiments, two liver cancer cell lines were stably overexpressed and downregulated for TEAD4 to characterize its role in in vitro models, in terms of proliferation, migration and anchorage-independent growth. Results: TEAD4 was found overexpressed in a subset of HCCs in the TCGA dataset and its overexpression correlated with worst overall survival (p=0.03). The tissue microarray analysis showed a similar trend not only in the HCCs but also in cirrhotic tissues. The in vitro assays demonstrated that the overexpression of TEAD4 promoted tumour growth and migration as well as increased foci formation capacity. On the other hand, TEAD4 knockdown was able to revert the phenotype, suggesting a putative oncogenic role of TEAD4 in hepatocarcinogenesis. Conclusions: Finally, TEAD4 is frequently overexpressed in HCCs and in cirrhotic tissues and its expression is associated with poor prognosis. Furthermore, in vitro evidence suggests that TEAD4 may act as oncogene and may have a pivotal role in hepatocarcinogenesis. Citation Format: Nadia Tosti, Manuela Lanzafame, Viola Paradiso, Charlotte K. Ng, Salvatore Piscuoglio, Cristina Quintavalle, Luigi Maria Terracciano. TEAD4 expression in human hepatocellular carcinoma correlates with poor prognosis and promotes tumor growth and migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3349.