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Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Knockout Decreases the Malignant Phenotype in Neuroblastoma Cell Lines

SIMPLE SUMMARY: Neuroblastoma is the most common extra-cranial tumor in children and despite medical advancements in cancer treatment, five-year survival for high-risk neuroblastoma remains less than 50%. Investigation of the mechanisms responsible for aggressive disease is necessary to identify nov...

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Autores principales: Bownes, Laura V, Williams, Adele P, Marayati, Raoud, Quinn, Colin H, Hutchins, Sara C, Stewart, Jerry E, Vu, Trung, Easlick, Juliet L, Mroczek-Musulman, Elizabeth, Crossman, David K, Anderson, Joshua C, Willey, Christopher D, Datta, Pran K, Beierle, Elizabeth A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268080/
https://www.ncbi.nlm.nih.gov/pubmed/34206917
http://dx.doi.org/10.3390/cancers13133201
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author Bownes, Laura V
Williams, Adele P
Marayati, Raoud
Quinn, Colin H
Hutchins, Sara C
Stewart, Jerry E
Vu, Trung
Easlick, Juliet L
Mroczek-Musulman, Elizabeth
Crossman, David K
Anderson, Joshua C
Willey, Christopher D
Datta, Pran K
Beierle, Elizabeth A
author_facet Bownes, Laura V
Williams, Adele P
Marayati, Raoud
Quinn, Colin H
Hutchins, Sara C
Stewart, Jerry E
Vu, Trung
Easlick, Juliet L
Mroczek-Musulman, Elizabeth
Crossman, David K
Anderson, Joshua C
Willey, Christopher D
Datta, Pran K
Beierle, Elizabeth A
author_sort Bownes, Laura V
collection PubMed
description SIMPLE SUMMARY: Neuroblastoma is the most common extra-cranial tumor in children and despite medical advancements in cancer treatment, five-year survival for high-risk neuroblastoma remains less than 50%. Investigation of the mechanisms responsible for aggressive disease is necessary to identify novel therapeutic targets and improve survival. Serine-threonine kinase receptor associated protein (STRAP) is upregulated in several malignancies and plays an important role in tumor growth and metastasis. The role of STRAP in pediatric malignancies and specifically in neuroblastoma has not been explored. We sought to determine whether STRAP functions assisted to promote the malignant phenotype in neuroblastoma and could provide a potential target for future therapies. ABSTRACT: Background: Serine-threonine kinase receptor-associated protein (STRAP) plays an important role in neural development but also in tumor growth. Neuroblastoma, a tumor of neural crest origin, is the most common extracranial solid malignancy of childhood and it continues to carry a poor prognosis. The recent discovery of the role of STRAP in another pediatric solid tumor, osteosarcoma, and the known function of STRAP in neural development, led us to investigate the role of STRAP in neuroblastoma tumorigenesis. Methods: STRAP protein expression was abrogated in two human neuroblastoma cell lines, SK-N-AS and SK-N-BE(2), using transient knockdown with siRNA, stable knockdown with shRNA lentiviral transfection, and CRISPR-Cas9 genetic knockout. STRAP knockdown and knockout cells were examined for phenotypic alterations in vitro and tumor growth in vivo. Results: Cell proliferation, motility, and growth were significantly decreased in STRAP knockout compared to wild-type cells. Indicators of stemness, including mRNA abundance of common stem cell markers Oct4, Nanog, and Nestin, the percentage of cells expressing CD133 on their surface, and the ability to form tumorspheres were significantly decreased in the STRAP KO cells. In vivo, STRAP knockout cells formed tumors less readily than wild-type tumor cells. Conclusion: These novel findings demonstrated that STRAP plays a role in tumorigenesis and maintenance of neuroblastoma stemness.
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spelling pubmed-82680802021-07-10 Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Knockout Decreases the Malignant Phenotype in Neuroblastoma Cell Lines Bownes, Laura V Williams, Adele P Marayati, Raoud Quinn, Colin H Hutchins, Sara C Stewart, Jerry E Vu, Trung Easlick, Juliet L Mroczek-Musulman, Elizabeth Crossman, David K Anderson, Joshua C Willey, Christopher D Datta, Pran K Beierle, Elizabeth A Cancers (Basel) Article SIMPLE SUMMARY: Neuroblastoma is the most common extra-cranial tumor in children and despite medical advancements in cancer treatment, five-year survival for high-risk neuroblastoma remains less than 50%. Investigation of the mechanisms responsible for aggressive disease is necessary to identify novel therapeutic targets and improve survival. Serine-threonine kinase receptor associated protein (STRAP) is upregulated in several malignancies and plays an important role in tumor growth and metastasis. The role of STRAP in pediatric malignancies and specifically in neuroblastoma has not been explored. We sought to determine whether STRAP functions assisted to promote the malignant phenotype in neuroblastoma and could provide a potential target for future therapies. ABSTRACT: Background: Serine-threonine kinase receptor-associated protein (STRAP) plays an important role in neural development but also in tumor growth. Neuroblastoma, a tumor of neural crest origin, is the most common extracranial solid malignancy of childhood and it continues to carry a poor prognosis. The recent discovery of the role of STRAP in another pediatric solid tumor, osteosarcoma, and the known function of STRAP in neural development, led us to investigate the role of STRAP in neuroblastoma tumorigenesis. Methods: STRAP protein expression was abrogated in two human neuroblastoma cell lines, SK-N-AS and SK-N-BE(2), using transient knockdown with siRNA, stable knockdown with shRNA lentiviral transfection, and CRISPR-Cas9 genetic knockout. STRAP knockdown and knockout cells were examined for phenotypic alterations in vitro and tumor growth in vivo. Results: Cell proliferation, motility, and growth were significantly decreased in STRAP knockout compared to wild-type cells. Indicators of stemness, including mRNA abundance of common stem cell markers Oct4, Nanog, and Nestin, the percentage of cells expressing CD133 on their surface, and the ability to form tumorspheres were significantly decreased in the STRAP KO cells. In vivo, STRAP knockout cells formed tumors less readily than wild-type tumor cells. Conclusion: These novel findings demonstrated that STRAP plays a role in tumorigenesis and maintenance of neuroblastoma stemness. MDPI 2021-06-26 /pmc/articles/PMC8268080/ /pubmed/34206917 http://dx.doi.org/10.3390/cancers13133201 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bownes, Laura V
Williams, Adele P
Marayati, Raoud
Quinn, Colin H
Hutchins, Sara C
Stewart, Jerry E
Vu, Trung
Easlick, Juliet L
Mroczek-Musulman, Elizabeth
Crossman, David K
Anderson, Joshua C
Willey, Christopher D
Datta, Pran K
Beierle, Elizabeth A
Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Knockout Decreases the Malignant Phenotype in Neuroblastoma Cell Lines
title Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Knockout Decreases the Malignant Phenotype in Neuroblastoma Cell Lines
title_full Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Knockout Decreases the Malignant Phenotype in Neuroblastoma Cell Lines
title_fullStr Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Knockout Decreases the Malignant Phenotype in Neuroblastoma Cell Lines
title_full_unstemmed Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Knockout Decreases the Malignant Phenotype in Neuroblastoma Cell Lines
title_short Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Knockout Decreases the Malignant Phenotype in Neuroblastoma Cell Lines
title_sort serine-threonine kinase receptor-associated protein (strap) knockout decreases the malignant phenotype in neuroblastoma cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268080/
https://www.ncbi.nlm.nih.gov/pubmed/34206917
http://dx.doi.org/10.3390/cancers13133201
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