Abstract B149: Yes-associated protein (YAP) is associated with aggressive characteristics of BRAFV600E thyroid cancer.

Abstract

Abstract Up regulation of Yes-associated protein (YAP), a transcriptional co-activator regulated by Hippo (MST-LAST-YAP) pathway, has been reported to mediate oncogenic transformation in animal models of hepatocellular carcinomas. However, the expression status and molecular biological role of YAP in thyroid cancer remained to be investigated. We evaluated YAP expression and identified increased nuclear YAP expression in PTC and ATC. Interestingly, we could observe nuclear YAP staining more frequently in BRAFV600E(+) PTC. We also performed immunofluorescence staining to verify intracellular localization of YAP in TPC1 (harboring RET/PTC1), 8505C (harboring BRAFV600E) and BRAFV600E stably transfected HEK293T cells. Consistently, we could detect nuclear YAP in 8505C and BRAFV600E expressed cells, but not in TPC1. Although cell viability assays did not show any difference between YAP knockout cells and control cells generated by using shYAP in 8505C and shCTL (control) 8505C, YAP knockout cells showed remarkably decreased migration ability in the scratch assays. Using orthotopic mice models, shYAP 8505C injected mice showed decreased local invasion ability and less frequent lung metastasis. In conclusions, Nuclear YAP could be more frequently detected in BRAFV600E(+) thyroid cancer compared to BRAFV600E(−) thyroid cancer. Furthermore, nuclear YAP in BRAFV600E(+) thyroid cancer was associated with local invasiveness and distant metastasis, presenting that YAP could affect the aggressive phenotype of BRAFV600E(+) thyroid cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B149.