Abstract
Yes-associated protein 1 (YAP1) stimulates cell proliferation, epithelial-to-mesenchymal transition, invasion and metastasis in several cancers. Here, we investigated the involvement of YAP1 in papillary thyroid carcinoma (PTC) by assessing YAP1 mRNA and protein levels in PTC tissues and matched normal thyroid epithelial tissues from 50 patients. YAP1 mRNA and protein levels were higher in PTC tumor tissues than in control tissues, and correlated positively with the levels of proliferation-related genes (KI67 and c-MYC). We also used lentiviral vectors to overexpress or silence YAP1 expression in the K1 PTC cell line so that we could investigate the effects of YAP1 on cancer cell proliferation. YAP1 overexpression enhanced PTC cell proliferation by activating ERK1/2 and AKT, and these effects were impaired by treating the cells with the MEK inhibitor U0126 or the AKT inhibitor GSK690693. Finally, YAP1 overexpression dramatically induced growth of tumors from PTC cells in a xenograft mouse model. These results suggest that YAP1 enhances cell proliferation in PTC, and thus may be a promising target in the treatment of PTC.
Highlights
The incidence of thyroid carcinoma is increasing by 4% per year, and papillary thyroid carcinoma (PTC) accounts for approximately 80% of thyroid carcinoma cases [1]
We found that Yes-associated protein 1 (YAP1) levels were elevated in human PTC tissues and a PTC cell line
A positive correlation was observed between the expression of YAP1 and the expression of proliferation-related genes (KI67 and c-MYC) in tumor specimens
Summary
The incidence of thyroid carcinoma is increasing by 4% per year, and papillary thyroid carcinoma (PTC) accounts for approximately 80% of thyroid carcinoma cases [1]. Like the majority of malignancies, thyroid carcinomas are usually associated with specific genetic abnormalities that cause aberrant cell proliferation [2]. Knowledge of signaling networks has become increasingly important for our understanding of cell proliferation. YAP1 is known to promote cell proliferation, epithelial-to-mesenchymal transition, invasion and metastasis [4]. Multiple studies have demonstrated that YAP1 is overexpressed in various types of solid tumors, including breast [5], hepatocellular [6] tumors. In these cancers, high YAP1 expression is associated with tumor initiation, invasion and metastasis, suggesting that YAP1 promotes tumorigenesis
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