Abstract 826: Yes-associated protein increases hepatocellular carcinoma chemosensitivity by modulating p53

Abstract

Abstract The function of the yes-associated protein (YAP) transcription co-activator remains an enigma since reports indicate that YAP either acts as an oncogene or enhances apoptosis. In this study, we found that YAP expression occurs in 51% of human hepatocellular carcinoma (HCC) biopsies while phosphorylated YAP (pYAP) expression occurs in 33% of Grade II and III HCCs. In addition, we found that YAP and p53 expression/ nuclear translocation increase in chemo-treated HepG2 cells. In chemo-treated HepG2 cells transfected with WT-YAP or blank (control), the chemosensitivity of the HepG2 + WT-YAP cells increases compared to HepG2+blank cells. In chemo-treated HepG2 cells transfected with Flag-S94A (TEAD binding domain mutant), Flag-W1W2 (WW domain mutant), or blank (control), the chemosensitivity and p53 expression/ nuclear translocation of the HepG2+Flag-S94A cells and HepG2+Flag-W1W2 cells decrease compared to HepG2+blank cells. In chemo-treated HepG2 cells transfected with Flag-5SA-S94A or Flag-5SA-W1W2, the chemosensitivity and p53 expression/ nuclear translocation of the HepG2+Flag-5SA-S94A cells and HepG2+Flag-5SA-W1W2 cells increase again compared to HepG2+Flag-S94A cells or HepG2+Flag-W1W2 cells respectively. These results indicate that YAP promotes chemosensitivity by modulating p53 during chemo-treatment, and YAP-modulated p53 activity requires the TEAD binding domain and the WW domain. In summary, our data indicate that YAP functions as a tumor-suppressor that enhances apoptosis by modulating p53 activity during chemo-treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 826. doi:1538-7445.AM2012-826