RAF kinase inhibitor-independent constitutive activation of Yes-associated protein 1 promotes tumor progression in thyroid cancer
| العنوان: | RAF kinase inhibitor-independent constitutive activation of Yes-associated protein 1 promotes tumor progression in thyroid cancer |
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| المؤلفون: | J.U. Lee, Sungjin Kim, Young Suk Jo, Dae-Sik Lim, K.S. Kim, Yong Kyung Kim, Jong Man Kim, Minho Shong, J.W. Kim, Sunhee Lee, Miae Lee, Min Jeong Ryu, M.J. Choi, Y.W. Koh |
| المصدر: | Oncogenesis ONCOGENESIS(2) |
| بيانات النشر: | Nature Publishing Group, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | YAP1, Yes-associated protein 1, Cancer Research, Mutation, orthotopic model, drug resistance, endocrine system diseases, business.industry, molecular targeted therapy, MEK inhibitor, Raf Kinase Inhibitor, medicine.disease, medicine.disease_cause, Tumor progression, proto-oncogene proteins B-Raf, thyroidneoplasm, medicine, Cancer research, Gene silencing, Original Article, Anaplastic thyroid cancer, business, Molecular Biology, Thyroid cancer, thyroid neoplasm |
| الوصف: | The transcription coactivator Yes-associated protein 1 (YAP1) is regulated by the Hippo tumor suppressor pathway. However, the role of YAP1 in thyroid cancer, which is frequently associated with the BRAF(V600E) mutation, remains unknown. This study aimed to investigate the role of YAP1 in thyroid cancer. YAP1 was overexpressed in papillary (PTC) and anaplastic thyroid cancer, and nuclear YAP1 was more frequently detected in BRAF(V600E) (+) PTC. In the thyroid cancer cell lines TPC-1 and HTH7, which do not have the BRAF(V600E) mutation, YAP1 was cytosolic and inactive at high cell densities. In contrast, YAP1 was retained in the nucleus and its target genes were expressed in the thyroid cancer cells 8505C and K1, which harbor the BRAF(V600E) mutation, regardless of cell density. Furthermore, the nuclear activation of YAP1 in 8505C was not inhibited by RAF or MEK inhibitor. In vitro experiments, YAP1 silencing or overexpression affected migratory capacities of 8505C and TPC-1 cells. YAP1 knockdown resulted in marked decrease of tumor volume, invasion and distant metastasis in orthotopic tumor xenograft mouse models using the 8505C thyroid cancer cell line. Taken together, YAP1 is involved in the tumor progression of thyroid cancer and YAP1-mediated effects might not be affected by the currently used RAF kinase inhibitors. |
| اللغة: | English |
| تدمد: | 2157-9024 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91cfb66a61d55e317cbb2c917e7e65d1 http://europepmc.org/articles/PMC3740284 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....91cfb66a61d55e317cbb2c917e7e65d1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 21579024 |
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