RAF kinase inhibitor-independent constitutive activation of Yes-associated protein 1 promotes tumor progression in thyroid cancer

S. E. Lee, J. U. Lee, M. H. Lee, M. J. Ryu, S. J. Kim, Y. K. Kim, M. J. Choi, K. S. Kim, J. M. Kim, J. W. Kim, Y. W. Koh, D. S. Lim, Y. S. Jo, M. Shong

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Abstract

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 BRAFV600E 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 BRAFV600E (+) 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 BRAFV600E 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.

Original languageEnglish
Article numbere55
JournalOncogenesis
Volume2
DOIs
Publication statusPublished - 2013 Jul 29

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Thyroid Neoplasms
Phosphotransferases
Neoplasms
Proteins
Factor IX
Mutation
Cell Count
Cell Line
Mitogen-Activated Protein Kinase Kinases
Tumor Burden
Heterografts
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

Cite this

Lee, S. E. ; Lee, J. U. ; Lee, M. H. ; Ryu, M. J. ; Kim, S. J. ; Kim, Y. K. ; Choi, M. J. ; Kim, K. S. ; Kim, J. M. ; Kim, J. W. ; Koh, Y. W. ; Lim, D. S. ; Jo, Y. S. ; Shong, M. / RAF kinase inhibitor-independent constitutive activation of Yes-associated protein 1 promotes tumor progression in thyroid cancer. In: Oncogenesis. 2013 ; Vol. 2.
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abstract = "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 BRAFV600E 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 BRAFV600E (+) 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 BRAFV600E 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.",
author = "Lee, {S. E.} and Lee, {J. U.} and Lee, {M. H.} and Ryu, {M. J.} and Kim, {S. J.} and Kim, {Y. K.} and Choi, {M. J.} and Kim, {K. S.} and Kim, {J. M.} and Kim, {J. W.} and Koh, {Y. W.} and Lim, {D. S.} and Jo, {Y. S.} and M. Shong",
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Lee, SE, Lee, JU, Lee, MH, Ryu, MJ, Kim, SJ, Kim, YK, Choi, MJ, Kim, KS, Kim, JM, Kim, JW, Koh, YW, Lim, DS, Jo, YS & Shong, M 2013, 'RAF kinase inhibitor-independent constitutive activation of Yes-associated protein 1 promotes tumor progression in thyroid cancer', Oncogenesis, vol. 2, e55. https://doi.org/10.1038/oncsis.2013.12

RAF kinase inhibitor-independent constitutive activation of Yes-associated protein 1 promotes tumor progression in thyroid cancer. / Lee, S. E.; Lee, J. U.; Lee, M. H.; Ryu, M. J.; Kim, S. J.; Kim, Y. K.; Choi, M. J.; Kim, K. S.; Kim, J. M.; Kim, J. W.; Koh, Y. W.; Lim, D. S.; Jo, Y. S.; Shong, M.

In: Oncogenesis, Vol. 2, e55, 29.07.2013.

Research output: Contribution to journalArticle

TY - JOUR

T1 - RAF kinase inhibitor-independent constitutive activation of Yes-associated protein 1 promotes tumor progression in thyroid cancer

AU - Lee, S. E.

AU - Lee, J. U.

AU - Lee, M. H.

AU - Ryu, M. J.

AU - Kim, S. J.

AU - Kim, Y. K.

AU - Choi, M. J.

AU - Kim, K. S.

AU - Kim, J. M.

AU - Kim, J. W.

AU - Koh, Y. W.

AU - Lim, D. S.

AU - Jo, Y. S.

AU - Shong, M.

PY - 2013/7/29

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