Expression of YAP1 in aggressive thyroid cancer

The Hippo signal transduction pathway plays a crucial role in the control of cellular proliferation, and its deregulation is believed to be involved in neoplastic transformation [ 1 , 2 ]. A wide array of human cancers show a down-regulation of Hippo pathway, resulting in the activation of the co- transcription factors Yes-associated protein 1 (YAP1) and Transcriptional coactivator with PDZ-binding motif (TAZ). In turn, the YAP/TAZ complex increases transcription of target proteins with oncogenic activity [ 1 , 2 ]. Thus, target- ing YAP1 has been tested to arrest cancer cell proliferation [ 3 , 4 ]. Increased expression and/or nuclear accumulation of YAP1 has been described also in thyroid cancer tissues and cell lines [ 5 , 6 ]. In particular, Lee et al. found that YAP1 was overexpressed in the nucleus and cytoplasm of papil- lary (PTC) and anaplastic thyroid cancers (ATC), with a higher frequency in those carrying a V600E BRAF muta- tion [ 5 ]. By silencing YAP1 in orthotopic xenograft models of thyroid cancer, they also demonstrated an involvement of YAP1 in tumor progression and resistance to RAF kinase inhibitors [ 5 ]. An oncogenic role of YAP1, played by transactivation of RAS proteins, was also reported in other preclinical models of thyroid cancer [ 6 ]. No information is available about the expression of YAP in medullary thyroid cancer (MTC). In this work, we investigated the expression of YAP1 in a series of thyroid neoplasia, including 43 PTCs classi fi ed as low/intermediate/high risk according to ATA criteria [ 7 ] and eight lymph node metastases of PTCs (LN), extending our analysis to 15 MTCs. An additional cohort of 34 low/ intermediate risk PTCs was used to analyze the expression of two target genes activated by YAP1.The Hippo signal transduction pathway plays a crucial role in the control of cellular proliferation, and its deregulation is believed to be involved in neoplastic transformation [ 1 , 2 ]. A wide array of human cancers show a down-regulation of Hippo pathway, resulting in the activation of the co- transcription factors Yes-associated protein 1 (YAP1) and Transcriptional coactivator with PDZ-binding motif (TAZ). In turn, the YAP/TAZ complex increases transcription of target proteins with oncogenic activity [ 1 , 2 ]. Thus, target- ing YAP1 has been tested to arrest cancer cell proliferation [ 3 , 4 ]. Increased expression and/or nuclear accumulation of YAP1 has been described also in thyroid cancer tissues and cell lines [ 5 , 6 ]. In particular, Lee et al. found that YAP1 was overexpressed in the nucleus and cytoplasm of papil- lary (PTC) and anaplastic thyroid cancers (ATC), with a higher frequency in those carrying a V600E BRAF muta- tion [ 5 ]. By silencing YAP1 in orthotopic xenograft models of thyroid cancer, they also demonstrated an involvement of YAP1 in tumor progression and resistance to RAF kinase inhibitors [ 5 ]. An oncogenic role of YAP1, played by transactivation of RAS proteins, was also reported in other preclinical models of thyroid cancer [ 6 ]. No information is available about the expression of YAP in medullary thyroid cancer (MTC). In this work, we investigated the expression of YAP1 in a series of thyroid neoplasia, including 43 PTCs classi fi ed as low/intermediate/high risk according to ATA criteria [ 7 ] and eight lymph node metastases of PTCs (LN), extending our analysis to 15 MTCs. An additional cohort of 34 low/ intermediate risk PTCs was used to analyze the expression of two target genes activated by YAP1.