Abstract 1015: Head and neck cancer expression of YAP65: A novel oncogene

Abstract

Abstract Yes-associated protein (YAP), a transcription coactivator associated with maintaining tissue size, is reported as an oncogene in many types of cancer including ovarian, liver, lung, colon and prostate. However, the role of YAP in head and neck carcinomas is not known. Our objective was to explore the role of YAP in head and neck carcinomas. We found YAP overexpressed in the epithelial and stromal compartments of head and neck carcinomas compared to benign tissues in 140 samples. Interestingly, the squamous cell carcinomas, had elevated YAP expression in the epithelial cytoplasm in 36% of the patients. However, we observed both cytoplasmic and prominently nuclear localization of YAP in the adenocarcinomas. The tumor microenvironment is widely accepted as a promoter of tumor progression, where carcinoma-associated fibroblasts (CAFs) constitute the majority of cells. In the stroma, YAP was found to be expressed in endothelial cells and some heterogenously within the CAF population. As reported for prostate cancer, we found the transforming growth factor-beta (TGF-ß) receptor type II expression to be lost in the head and neck cancer-associated stromal cells. Since YAP has never been reported to be associated with CAFs, we performed in vitro experiment to determine the relationship of YAP and TGF-ß signaling in primary stromal cells associated with benign and head and neck cancer cells. We found TGF-ß1 can promote YAP expression and nuclear localization in normal fibroblasts. The oral human CAFs have differential expression of YAP and α-smooth muscle actin (α-SMA). Although CAFs are commonly characterized by their expression of α-SMA, YAP-expressing CAFs expressed less α-SMA and α-SMA-expressing CAFs expressed less YAP in seven independent CAF lines developed. However, all of these heterougenous head and neck CAF lines had the loss of TGF-ß receptor type II expression and concomitant upregulation of Wnt5a. Interestingly, those CAFs expressing YAP had 2-fold greater Wnt5a expression. In conclusion YAP expression is differentially expressed in adeno- and squamous cell carcinomas of head and neck carcinomas, and is heterogenously expressed in the associated CAF. YAP may regulate Wnt5a as a paracrine factor, reported to promote the progression of oral carcinomas, in a TGF-ß dependent and independent manner. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1015.