Studying the Role of Yes-Associated Protein in Oral Cancer

Abstract

Oral cancer is one of the most common cancer types worldwide with a 5-year survival rate less than 50 % for advanced diseases In Taiwan oral cancer is the 5th leading cause of cancer death which predominantly occurs among males Whole-genome copy number profiling revealed that around 10 % of advanced-stage oral cancer patients with tobacco and alcohol habituates had DNA amplifications in chromosome region 11q22 1-22 2 The gain of this region was shown to be one of the strongest predictors for poor clinical outcome for this cancer type One of the genes in this locus is Yes-associated protein (YAP) previously shown to control organ size and participate in the mediation of apoptosis A dual function tumor promoter or suppressor for YAP has been proposed in different cancer types Moreover YAP was also revealed as a vital requirement for yolk sac vasculogenesis and its overexpression in mouse endothelial cells enhanced angiogenic sprouting Together these data provide a strong linkage between YAP and angiogenesis although the detailed mechanism remains elusive We thus aimed to investigate the role of YAP in oral cancer progression and the relationship between YAP and tumor angiogenesis Our data demonstrated that YAP knockdown significantly impaired oral cancer cell proliferation migration and Matrigel invasion The knockdown also decreased xenograft tumorigenesis in vivo By contrast YAP overexpression showed a significant increase in oral cancer cell proliferation migration and Matrigel invasion These data revealed an oncogenic role of YAP in oral cancer A significant reduction of VEGF-A and bFGF mRNA expression in the YAP-depleted oral cancer cells may partly account for the attenuating effect of YAP-depleted conditioned medium (CM) on endothelial proliferation and Matrigel tube formation Consistent with the notion that YAP mediates angiogenesis YAP/TEAD complex modulated the transcriptional regulation of VEGF-A and bFGF by directly interacting with their promoters bearing TEAD-binding sites in oral cancer cells Although more studies are needed our ?ndings potentially shed mechanistic light on YAP-mediated oncogenic action through both autocrine and paracrine fashions in oral cancer cells

Date of Award	2016 Aug 30
Original language	English
Supervisor	Li-Wha Wu (Supervisor)