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Targeting Focal Adhesion Kinase Suppresses the Malignant Phenotype in Rhabdomyosarcoma Cells()
Despite the tremendous advances in the treatment of childhood solid tumors, rhabdomyosarcoma (RMS) continues to provide a therapeutic challenge. Children with metastatic or relapsed disease have a disease-free survival rate under 30%. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925808/ https://www.ncbi.nlm.nih.gov/pubmed/27567948 http://dx.doi.org/10.1016/j.tranon.2016.06.001 |
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author | Waters, Alicia M. Stafman, Laura L. Garner, Evan F. Mruthyunjayappa, Smitha Stewart, Jerry E. Mroczek-Musulman, Elizabeth Beierle, Elizabeth A. |
author_facet | Waters, Alicia M. Stafman, Laura L. Garner, Evan F. Mruthyunjayappa, Smitha Stewart, Jerry E. Mroczek-Musulman, Elizabeth Beierle, Elizabeth A. |
author_sort | Waters, Alicia M. |
collection | PubMed |
description | Despite the tremendous advances in the treatment of childhood solid tumors, rhabdomyosarcoma (RMS) continues to provide a therapeutic challenge. Children with metastatic or relapsed disease have a disease-free survival rate under 30%. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is important in many facets of tumorigenesis. Signaling pathways both upstream and downstream to FAK have been found to be important in sarcoma tumorigenesis, leading us to hypothesize that FAK would be present in RMS and would impact cellular survival. In the current study, we showed that FAK was present and phosphorylated in pediatric alveolar and embryonal RMS tumor specimens and cell lines. We also examined the effects of FAK inhibition upon two RMS cell lines utilizing parallel approaches including RNAi and small molecule inhibitors. FAK inhibition resulted in decreased cellular survival, invasion, and migration and increased apoptosis. Furthermore, small molecule inhibition of FAK led to decreased tumor growth in a nude mouse RMS xenograft model. The findings from this study will help to further our understanding of the regulation of tumorigenesis in RMS and may provide desperately needed novel therapeutic strategies for these difficult-to-treat tumors. |
format | Online Article Text |
id | pubmed-4925808 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-49258082016-07-13 Targeting Focal Adhesion Kinase Suppresses the Malignant Phenotype in Rhabdomyosarcoma Cells() Waters, Alicia M. Stafman, Laura L. Garner, Evan F. Mruthyunjayappa, Smitha Stewart, Jerry E. Mroczek-Musulman, Elizabeth Beierle, Elizabeth A. Transl Oncol Original article Despite the tremendous advances in the treatment of childhood solid tumors, rhabdomyosarcoma (RMS) continues to provide a therapeutic challenge. Children with metastatic or relapsed disease have a disease-free survival rate under 30%. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is important in many facets of tumorigenesis. Signaling pathways both upstream and downstream to FAK have been found to be important in sarcoma tumorigenesis, leading us to hypothesize that FAK would be present in RMS and would impact cellular survival. In the current study, we showed that FAK was present and phosphorylated in pediatric alveolar and embryonal RMS tumor specimens and cell lines. We also examined the effects of FAK inhibition upon two RMS cell lines utilizing parallel approaches including RNAi and small molecule inhibitors. FAK inhibition resulted in decreased cellular survival, invasion, and migration and increased apoptosis. Furthermore, small molecule inhibition of FAK led to decreased tumor growth in a nude mouse RMS xenograft model. The findings from this study will help to further our understanding of the regulation of tumorigenesis in RMS and may provide desperately needed novel therapeutic strategies for these difficult-to-treat tumors. Neoplasia Press 2016-06-24 /pmc/articles/PMC4925808/ /pubmed/27567948 http://dx.doi.org/10.1016/j.tranon.2016.06.001 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Waters, Alicia M. Stafman, Laura L. Garner, Evan F. Mruthyunjayappa, Smitha Stewart, Jerry E. Mroczek-Musulman, Elizabeth Beierle, Elizabeth A. Targeting Focal Adhesion Kinase Suppresses the Malignant Phenotype in Rhabdomyosarcoma Cells() |
title | Targeting Focal Adhesion Kinase Suppresses the Malignant Phenotype in Rhabdomyosarcoma Cells() |
title_full | Targeting Focal Adhesion Kinase Suppresses the Malignant Phenotype in Rhabdomyosarcoma Cells() |
title_fullStr | Targeting Focal Adhesion Kinase Suppresses the Malignant Phenotype in Rhabdomyosarcoma Cells() |
title_full_unstemmed | Targeting Focal Adhesion Kinase Suppresses the Malignant Phenotype in Rhabdomyosarcoma Cells() |
title_short | Targeting Focal Adhesion Kinase Suppresses the Malignant Phenotype in Rhabdomyosarcoma Cells() |
title_sort | targeting focal adhesion kinase suppresses the malignant phenotype in rhabdomyosarcoma cells() |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4925808/ https://www.ncbi.nlm.nih.gov/pubmed/27567948 http://dx.doi.org/10.1016/j.tranon.2016.06.001 |
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