Focal Adhesion Kinase Inhibition Contributes to Tumor Cell Survival and Motility in Neuroblastoma Patient-Derived Xenografts

Abstract Patient-derived xenografts (PDXs) provide an opportunity to evaluate the effects of therapies in an environment that more closely resembles the human condition than that seen with long-term passage cell lines. In the current studies, we investigated the effects of FAK inhibition on two neur...

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Autores principales:	Laura L. Stafman, Adele P. Williams, Raoud Marayati, Jamie M. Aye, Hooper R. Markert, Evan F. Garner, Colin H. Quinn, Shoeb B. Lallani, Jerry E. Stewart, Karina J. Yoon, Kimberly Whelan, Elizabeth A. Beierle
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ae4c4e6cac14422ea46500505cb9f16e
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spelling	oai:doaj.org-article:ae4c4e6cac14422ea46500505cb9f16e2021-12-02T15:09:45ZFocal Adhesion Kinase Inhibition Contributes to Tumor Cell Survival and Motility in Neuroblastoma Patient-Derived Xenografts10.1038/s41598-019-49853-z2045-2322https://doaj.org/article/ae4c4e6cac14422ea46500505cb9f16e2019-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-49853-zhttps://doaj.org/toc/2045-2322Abstract Patient-derived xenografts (PDXs) provide an opportunity to evaluate the effects of therapies in an environment that more closely resembles the human condition than that seen with long-term passage cell lines. In the current studies, we investigated the effects of FAK inhibition on two neuroblastoma PDXs in vitro. Cells were treated with two small molecule inhibitors of FAK, PF-573,228 (PF) and 1,2,4,5-benzentetraamine tetrahydrochloride (Y15). Following FAK inhibition, cell survival and proliferation decreased significantly and cell cycle arrest was seen in both cell lines. Migration and invasion assays were used to determine the effect of FAK inhibition on cell motility, which decreased significantly in both cell lines in the presence of either inhibitor. Finally, tumor cell stemness following FAK inhibition was evaluated with extreme limiting dilution assays as well as with immunoblotting and quantitative real-time PCR for the expression of stem cell markers. FAK inhibition decreased formation of tumorspheres and resulted in a corresponding decrease in established stem cell markers. FAK inhibition decreased many characteristics of the malignant phenotype, including cancer stem cell like features in neuroblastoma PDXs, making FAK a candidate for further investigation as a potential target for neuroblastoma therapy.Laura L. StafmanAdele P. WilliamsRaoud MarayatiJamie M. AyeHooper R. MarkertEvan F. GarnerColin H. QuinnShoeb B. LallaniJerry E. StewartKarina J. YoonKimberly WhelanElizabeth A. BeierleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Laura L. Stafman Adele P. Williams Raoud Marayati Jamie M. Aye Hooper R. Markert Evan F. Garner Colin H. Quinn Shoeb B. Lallani Jerry E. Stewart Karina J. Yoon Kimberly Whelan Elizabeth A. Beierle Focal Adhesion Kinase Inhibition Contributes to Tumor Cell Survival and Motility in Neuroblastoma Patient-Derived Xenografts
description	Abstract Patient-derived xenografts (PDXs) provide an opportunity to evaluate the effects of therapies in an environment that more closely resembles the human condition than that seen with long-term passage cell lines. In the current studies, we investigated the effects of FAK inhibition on two neuroblastoma PDXs in vitro. Cells were treated with two small molecule inhibitors of FAK, PF-573,228 (PF) and 1,2,4,5-benzentetraamine tetrahydrochloride (Y15). Following FAK inhibition, cell survival and proliferation decreased significantly and cell cycle arrest was seen in both cell lines. Migration and invasion assays were used to determine the effect of FAK inhibition on cell motility, which decreased significantly in both cell lines in the presence of either inhibitor. Finally, tumor cell stemness following FAK inhibition was evaluated with extreme limiting dilution assays as well as with immunoblotting and quantitative real-time PCR for the expression of stem cell markers. FAK inhibition decreased formation of tumorspheres and resulted in a corresponding decrease in established stem cell markers. FAK inhibition decreased many characteristics of the malignant phenotype, including cancer stem cell like features in neuroblastoma PDXs, making FAK a candidate for further investigation as a potential target for neuroblastoma therapy.
format	article
author	Laura L. Stafman Adele P. Williams Raoud Marayati Jamie M. Aye Hooper R. Markert Evan F. Garner Colin H. Quinn Shoeb B. Lallani Jerry E. Stewart Karina J. Yoon Kimberly Whelan Elizabeth A. Beierle
author_facet	Laura L. Stafman Adele P. Williams Raoud Marayati Jamie M. Aye Hooper R. Markert Evan F. Garner Colin H. Quinn Shoeb B. Lallani Jerry E. Stewart Karina J. Yoon Kimberly Whelan Elizabeth A. Beierle
author_sort	Laura L. Stafman
title	Focal Adhesion Kinase Inhibition Contributes to Tumor Cell Survival and Motility in Neuroblastoma Patient-Derived Xenografts
title_short	Focal Adhesion Kinase Inhibition Contributes to Tumor Cell Survival and Motility in Neuroblastoma Patient-Derived Xenografts
title_full	Focal Adhesion Kinase Inhibition Contributes to Tumor Cell Survival and Motility in Neuroblastoma Patient-Derived Xenografts
title_fullStr	Focal Adhesion Kinase Inhibition Contributes to Tumor Cell Survival and Motility in Neuroblastoma Patient-Derived Xenografts
title_full_unstemmed	Focal Adhesion Kinase Inhibition Contributes to Tumor Cell Survival and Motility in Neuroblastoma Patient-Derived Xenografts
title_sort	focal adhesion kinase inhibition contributes to tumor cell survival and motility in neuroblastoma patient-derived xenografts
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/ae4c4e6cac14422ea46500505cb9f16e
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Focal Adhesion Kinase Inhibition Contributes to Tumor Cell Survival and Motility in Neuroblastoma Patient-Derived Xenografts

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