Journal article
Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Knockout Decreases the Malignant Phenotype in Neuroblastoma Cell Lines
Cancers, Vol.13(13), p.3201
06/26/2021
DOI: 10.3390/cancers13133201
PMCID: PMC8268080
PMID: 34206917
Abstract
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. 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.
Details
- Title: Subtitle
- Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Knockout Decreases the Malignant Phenotype in Neuroblastoma Cell Lines
- Creators
- Laura Bownes - University of Alabama at BirminghamAdele P. Williams - University of AlabamaRaoud Marayati - University of Alabama at BirminghamColin H. Quinn - University of Alabama at BirminghamSara C. Hutchins - University of Alabama at BirminghamJerry E. Stewart - University of Alabama at BirminghamTrung Vu - University of Alabama at BirminghamJuliet L. Easlick - University of Alabama at BirminghamElizabeth Mroczek-Musulman - Childrens Alabama, Dept Pathol, Birmingham, AL 35233 USADavid K. Crossman - University of Alabama at BirminghamJoshua C. Anderson - University of Alabama at BirminghamChristopher D. Willey - University of Alabama at BirminghamPran K. Datta - University of Alabama at BirminghamElizabeth A. Beierle - University of Alabama at Birmingham
- Resource Type
- Journal article
- Publication Details
- Cancers, Vol.13(13), p.3201
- Publisher
- Mdpi
- DOI
- 10.3390/cancers13133201
- PMID
- 34206917
- PMCID
- PMC8268080
- ISSN
- 2072-6694
- eISSN
- 2072-6694
- Number of pages
- 21
- Grant note
- Sid Strong Foundation CA 118948 / UAB U54 Pilot Project Elaine Roberts Foundation Lombardi Cancer Research Fund/Starr Children's Fund Open Hearts Overflowing Hands T32 CA229102; T32 CA183926; T32 CA091078; 5T32GM008361; P30 AR048311; P30 AI27667; P30 CA013148 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 1I01BX005143 / Veterans Affairs Merit Review Award; US Department of Veterans Affairs
- Language
- English
- Date published
- 06/26/2021
- Academic Unit
- Stead Family Department of Pediatrics; Hematology/Oncology
- Record Identifier
- 9984701544502771
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