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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-08-01
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| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523316300481 |
| _version_ | 1818543966128177152 |
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| author | Alicia M. Waters Laura L. Stafman Evan F. Garner Smitha Mruthyunjayappa Jerry E. Stewart Elizabeth Mroczek-Musulman Elizabeth A. Beierle |
| author_facet | Alicia M. Waters Laura L. Stafman Evan F. Garner Smitha Mruthyunjayappa Jerry E. Stewart Elizabeth Mroczek-Musulman Elizabeth A. Beierle |
| author_sort | Alicia M. Waters |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-11T22:42:18Z |
| format | Article |
| id | doaj.art-b5bd3aaff2064b53b27bfa1b1025c3f5 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 1944-7124 |
| language | English |
| last_indexed | 2024-12-11T22:42:18Z |
| publishDate | 2016-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-b5bd3aaff2064b53b27bfa1b1025c3f52022-12-22T00:47:46ZengElsevierTranslational Oncology1936-52331944-71242016-08-019426327310.1016/j.tranon.2016.06.001Targeting Focal Adhesion Kinase Suppresses the Malignant Phenotype in Rhabdomyosarcoma CellsAlicia M. Waters0Laura L. Stafman1Evan F. Garner2Smitha Mruthyunjayappa3Jerry E. Stewart4Elizabeth Mroczek-Musulman5Elizabeth A. Beierle6Department of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, ALDepartment of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, ALDepartment of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, ALDepartment of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, ALDepartment of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, ALDepartment of Pathology, University of Alabama, Birmingham, ALDepartment of Surgery, Division of Pediatric Surgery, University of Alabama, Birmingham, ALDespite 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.http://www.sciencedirect.com/science/article/pii/S1936523316300481 |
| spellingShingle | Alicia M. Waters Laura L. Stafman Evan F. Garner Smitha Mruthyunjayappa Jerry E. Stewart Elizabeth Mroczek-Musulman Elizabeth A. Beierle Targeting Focal Adhesion Kinase Suppresses the Malignant Phenotype in Rhabdomyosarcoma Cells Translational Oncology |
| 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 |
| url | http://www.sciencedirect.com/science/article/pii/S1936523316300481 |
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