Abstract 6206: The xl313 cryptic collagen epitope regulates ovarian tumor growth by a yap dependent mechanism

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Abstract Structural changes in the extra cellular matrix (ECM) can lead to the exposure of cryptic regulatory sites that play important roles in angiogenesis, inflammation, tumor growth, and tumor metastasis. Previously, we discovered that a unique cryptic regulatory site (XL313 cryptic epitope) containing the amino acid sequence RGDKGE, is generated during tumor development, and we found that this collagen epitope promotes angiogenesis and inflammation in vivo. Here, we provide the first evidence that ovarian carcinoma cells can bind the XL313 collagen epitope through integrin alpha-V beta-3 and that selectively blocking cellular interactions with the XL313 epitope significantly inhibits ovarian tumor growth and the formation of ascites fluid in vivo. To understand the cellular mechanism(s) by which antagonists of the XL313 epitope inhibit these pathological processes, we examined down-stream signaling events that were altered following blocking ovarian tumor cell interaction with the XL313 collagen epitope. Importantly, selectively targeting the XL313 epitope significantly reduced nuclear accumulation of the transcriptional co-activator YAP. In addition, blocking cellular interaction with the XL313 epitope resulted in enhanced YAP phosphorylation at serine-127. Interestingly, specific targeting of the XL313 epitope also enhanced LATS1 phosphorylation, which is a key effector molecule in the hippo- signaling pathway. Taken together, our data provide new cellular and molecular insight for understanding the role of the XL313 cryptic collagen epitope in controlling ovarian tumor growth, and suggest that selectively targeting the XL313 epitope-integrin-signaling cascade may represent a novel strategy to inhibit ovarian cancer progression. Citation Format: Xianghua Han, Jennifer M. Caron, Peter C. Brooks. The xl313 cryptic collagen epitope regulates ovarian tumor growth by a yap dependent mechanism [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6206.