In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 3338-3338
Abstract:
Ewing sarcoma is the second most common cancer of bone and soft tissue arising in children and young adults. Although the survival rate has improved for patients treated for localized disease, the survival rate for patients with metastatic tumor remains lower than 30%. In order to identify novel therapeutic targets and to better understand the genes involved in growth and survival of Ewing sarcoma, we employed a functional genomics approach based on siRNA screening. Four Ewing sarcoma cell lines, TC-32, TC-71, SK-ES-1 and RD-ES, were transfected with a library of siRNA targeting 287 cancer-associated genes. The resulting siRNA screening data for each cell line were normalized and statistical cut-offs were determined. The results indicated that siRNAs targeting Fibroblast Growth Factor Receptor 4, FGFR4 were among the most effective in reducing cell viability in all four of the Ewing sarcoma cell lines. Validation of the siRNA screens showed that siRNAs to FGFR4, reduced viability much greater that those to FGFR1, FGFR2, or FGFR3. Furthermore, siRNA targeting FGFR4 were able to induce caspase 3 activity. FGFR4 protein is expressed on Ewing sarcoma cells as determined by western blot analysis, although expression levels were lower compared to FGFR4 expression on rhabdomyosarcoma cells. Targeting FGFR activity in Ewing sarcoma cells using a pan-FGFR inhibitors PD-173074 and BGJ-398 demonstrated that Ewing sarcoma cells were sensitive to FGFR inhibition. Furthermore, treatment of Ewing sarcoma cells with the selective FGFR4 inhibitor BLU9931 resulted in growth inhibition and decreased ERK signaling. These results indicate that FGFR4 may play an important role in growth and survival of Ewing sarcoma and could serve as a potential therapeutic target for this disease. Citation Format: Justin J. Montoya, Daniel H. Wai, David W. Lee, Peter A. Azorsa, Oliver B. Pepper, Robert J. Arceci, David O. Azorsa. A role for FGFR4 in growth and survival of Ewing sarcoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3338. doi:10.1158/1538-7445.AM2017-3338
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-3338
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
