TEAD4 promotes tumorigenesis via regulation of HSP70B expression in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers with almost 800,000 deaths each year and increasing incidence. Despite the progress done in preventing, treating and improving patients’ life, incidence and mortality still rising. Surveillance programmes allow the diagnosis of early stage tumors that can benefit from therapies with curative intent such as resection, liver transplantation or local ablation. On the other hand, advanced HCC stages have limited benefit from chemoembolization and systemic treatments like sorafenib or regorafenib. Recent development of next generations sequence technologies has been useful to unveil the genetic and molecular landscape of HCC. However, the high heterogeneity of HCC together difficulties the development of more effective therapies. Thus, the identification of new molecular target is vital to develop more effective therapies for HCC patients.
TEAD4 is a member of the transcriptional enhancer factor family (TEF) that has been found dysregulated in different tumor entities. Several studies have validated its oncogenic role in the tumorigenic process by regulating key pathways involved in proliferation, migration and invasiveness. However, TEAD4 role in liver carcinogenesis remains still to be elucidate.
The present work demonstrated that TEAD4 promote hepatocarcinogenesis by regulating the transcription and the expression of HSP70B, member of the heat shock protein family. The evidence provided here suggest a novel mechanism inducing hepatocarcinogenesis that be exploit as new potential therapeutic target for HCC treatment.